ATGL肝脏组织特异性敲除小鼠的产生及其引起的渐进性脂肪肝机理研究
|
摘要
肝细胞胞质中甘油三酯(TG)的过多积累形成脂肪肝。脂肪肝是多种肝病包括肝硬化和肝癌的主要原因。目前,关于TG在肝细胞胞质中积累的代谢途径尤其是肝细胞的脂解尚不清楚,但有证据表明脂肪组织甘油三酯水解酶(ATGL)在脂解中发挥十分重要的作用。ATGL全身性敲除鼠肝脏积累脂肪,但由于此小鼠心脏积累过多脂肪而早期致死,因而无法进行肝脏脂解的研究。本论文首次创造了肝脏组织特异性ATGL敲除小鼠(ATGLLKO),通过系统的研究得出以下几点结果:
1.肝脏特异性ATGL缺失引起明显的脂肪肝,且脂肪肝的程度随年龄的增长而加重。组织形态学研究发现ATGLLKO小鼠肝脏脂滴呈明显的规律性分布:大脂滴分布于肝脏门静脉周边而小脂滴则主要集中于中心静脉周边。
2. ATGLLKO小鼠体重正常,并不肥胖,且DEXA扫描发现该小鼠的肌肉量显著高于对照组。血液指标检测显示,ATGLLKO小鼠的葡萄糖,TG和胆固醇水平和对照鼠相似。
3.除肝细胞外,ATGL缺失同时引起胆管上皮细胞脂质的大量积累,但血液GGT及ALP的水平正常。
4. ATGLLKO小鼠肝脏炎症细胞的分布和数量以及TNFα和IL-6的mRNA含量与对照组相似或低于对照。TUNEL染色显示,ATGLLKO小鼠与对照组肝脏凋亡细胞的数量相似。12月龄ATGLLKO肝脏Masson trichrome staining结果呈阴性。ATGLLKO小鼠肝脏内质网VLDL分泌正常。肝脏脂肪酸氧化试验显示β氧化水平和对照相比下降30%。
5.生理水平检测表明,ATGLLKO小鼠具有正常的葡萄糖和胰岛素耐受量以及以丙酮酸为底物的糖异生功能。肝脏水平上胰岛素刺激的Akt磷酸化水平正常。这些结果表明ATGLLKO小鼠具有正常的胰岛素敏感性。
6.尽管ATGLLKO小鼠的脂肪酸氧化下降30%,但48h饥饿条件下ATGLLKO小鼠与野生型鼠的呼吸交换率相似,同时ATGLLKO小鼠血液3-HB与对照组的升高水平相似,表明LKO小鼠完全可以满足应激状态下的能量需求。
7. ATGLLKO小鼠肝脏调控TG合成的重要酶DGAT2的mRNA水平下降了50倍;同时肝脏切片中溶酶体脂质体(lipolysosome)的数量增加了2.7倍,表明TG合成的降低以及溶酶体介导的TG的降解是缓解脂解缺陷的潜在补偿机制。
综上所述,肝脏ATGL缺失引起不伴随肥胖及代谢综合症的原发性脂肪肝。尽管ATGLLKO小鼠的脂肪肝高达20%,但肝脏依然维持正常的功能。ATGLLKO小鼠胆管内脂肪的累积并未影响其功能,表明ATGL也是胆管细胞重要的TG水解酶且无毒害作用。通过对溶酶体自噬作用的研究发现,溶酶体介导的肝细胞胞质中TG的降解是缓解脂肪肝的有效途径。与肥胖和糖尿病引起的脂肪肝相比,ATGL敲除引起的脂肪肝在代谢上具有缓解多种代谢综合症的保护作用,从而推测单纯性脂肪肝对机体起保护作用,而肥胖引起的继发性脂肪肝症状是机体在引发代谢综合症的前提下所产生的次级效应,因而ATGLLKO小鼠是研究脂肪肝以及其形成机理的理想模型。
Accumulation of cytoplasmic triacylglycerol (TG) underlies hepatic steatosis, a major cause of cirrhosis. The pathways of cytoplasmic TG metabolism are not well known in hepatocytes, but evidence suggests an important role in lipolysis for adipose triglyceride lipase (ATGL). We created mice with liver-specific inactivation of Pnpla2, the ATGL gene. These ATGLLKO mice had severe progressive periportal macrovesicular and pericentral microvesicular hepatic steatosis (73, 150 and 226μmol TG/g liver at 4, 8 and 12 months, respectively). However, plasma levels of glucose, TG and cholesterol were similar to controls’. Fasting 3-hydroxybutyrate level was normal, but in thin sections of liver, beta oxidation of palmitate was decreased by one third in ATGLLKO mice compared to controls. Tests of VLDL production, glucose and insulin tolerance and gluconeogenesis from pyruvate were normal. Plasma alanine aminotransferase levels were elevated in ATGLLKO mice but histological estimates of inflammation and fibrosis and mRNA levels of tumor necrosis factor-αand interleukin 6 were similar to or lower than in controls. ATGLLKO cholangiocytes also showed cytoplasmic lipid droplets, demonstrating that ATGL is also a major lipase in cholangiocytes. There was a 50-fold reduction of hepatic diacylglycerol acyltransferase 2 (DGAT2) mRNA level and a 2.7-fold increase of lipolysosomes in hepatocytes (p<0.001), suggesting reduced TG synthesis and increased lysosomal degradation of TG as potential compensatory mechanisms. Conclusion: Compared to the hepatic steatosis of obesity and diabetes, steatosis in ATGL deficiency is well tolerated metabolically. ATGLLKO mice will be useful for studying the pathophysiology of hepatic steatosis.
1.肝脏特异性ATGL缺失引起明显的脂肪肝,且脂肪肝的程度随年龄的增长而加重。组织形态学研究发现ATGLLKO小鼠肝脏脂滴呈明显的规律性分布:大脂滴分布于肝脏门静脉周边而小脂滴则主要集中于中心静脉周边。
2. ATGLLKO小鼠体重正常,并不肥胖,且DEXA扫描发现该小鼠的肌肉量显著高于对照组。血液指标检测显示,ATGLLKO小鼠的葡萄糖,TG和胆固醇水平和对照鼠相似。
3.除肝细胞外,ATGL缺失同时引起胆管上皮细胞脂质的大量积累,但血液GGT及ALP的水平正常。
4. ATGLLKO小鼠肝脏炎症细胞的分布和数量以及TNFα和IL-6的mRNA含量与对照组相似或低于对照。TUNEL染色显示,ATGLLKO小鼠与对照组肝脏凋亡细胞的数量相似。12月龄ATGLLKO肝脏Masson trichrome staining结果呈阴性。ATGLLKO小鼠肝脏内质网VLDL分泌正常。肝脏脂肪酸氧化试验显示β氧化水平和对照相比下降30%。
5.生理水平检测表明,ATGLLKO小鼠具有正常的葡萄糖和胰岛素耐受量以及以丙酮酸为底物的糖异生功能。肝脏水平上胰岛素刺激的Akt磷酸化水平正常。这些结果表明ATGLLKO小鼠具有正常的胰岛素敏感性。
6.尽管ATGLLKO小鼠的脂肪酸氧化下降30%,但48h饥饿条件下ATGLLKO小鼠与野生型鼠的呼吸交换率相似,同时ATGLLKO小鼠血液3-HB与对照组的升高水平相似,表明LKO小鼠完全可以满足应激状态下的能量需求。
7. ATGLLKO小鼠肝脏调控TG合成的重要酶DGAT2的mRNA水平下降了50倍;同时肝脏切片中溶酶体脂质体(lipolysosome)的数量增加了2.7倍,表明TG合成的降低以及溶酶体介导的TG的降解是缓解脂解缺陷的潜在补偿机制。
综上所述,肝脏ATGL缺失引起不伴随肥胖及代谢综合症的原发性脂肪肝。尽管ATGLLKO小鼠的脂肪肝高达20%,但肝脏依然维持正常的功能。ATGLLKO小鼠胆管内脂肪的累积并未影响其功能,表明ATGL也是胆管细胞重要的TG水解酶且无毒害作用。通过对溶酶体自噬作用的研究发现,溶酶体介导的肝细胞胞质中TG的降解是缓解脂肪肝的有效途径。与肥胖和糖尿病引起的脂肪肝相比,ATGL敲除引起的脂肪肝在代谢上具有缓解多种代谢综合症的保护作用,从而推测单纯性脂肪肝对机体起保护作用,而肥胖引起的继发性脂肪肝症状是机体在引发代谢综合症的前提下所产生的次级效应,因而ATGLLKO小鼠是研究脂肪肝以及其形成机理的理想模型。
Accumulation of cytoplasmic triacylglycerol (TG) underlies hepatic steatosis, a major cause of cirrhosis. The pathways of cytoplasmic TG metabolism are not well known in hepatocytes, but evidence suggests an important role in lipolysis for adipose triglyceride lipase (ATGL). We created mice with liver-specific inactivation of Pnpla2, the ATGL gene. These ATGLLKO mice had severe progressive periportal macrovesicular and pericentral microvesicular hepatic steatosis (73, 150 and 226μmol TG/g liver at 4, 8 and 12 months, respectively). However, plasma levels of glucose, TG and cholesterol were similar to controls’. Fasting 3-hydroxybutyrate level was normal, but in thin sections of liver, beta oxidation of palmitate was decreased by one third in ATGLLKO mice compared to controls. Tests of VLDL production, glucose and insulin tolerance and gluconeogenesis from pyruvate were normal. Plasma alanine aminotransferase levels were elevated in ATGLLKO mice but histological estimates of inflammation and fibrosis and mRNA levels of tumor necrosis factor-αand interleukin 6 were similar to or lower than in controls. ATGLLKO cholangiocytes also showed cytoplasmic lipid droplets, demonstrating that ATGL is also a major lipase in cholangiocytes. There was a 50-fold reduction of hepatic diacylglycerol acyltransferase 2 (DGAT2) mRNA level and a 2.7-fold increase of lipolysosomes in hepatocytes (p<0.001), suggesting reduced TG synthesis and increased lysosomal degradation of TG as potential compensatory mechanisms. Conclusion: Compared to the hepatic steatosis of obesity and diabetes, steatosis in ATGL deficiency is well tolerated metabolically. ATGLLKO mice will be useful for studying the pathophysiology of hepatic steatosis.
引文
Adams, L. A., Lymp, J. F., St Sauver, J., Sanderson, S. O., Lindor, K. D., Feldstein, A., Angulo, P. 2005. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology, 129(1):113-21.
Ahmadian, M., Duncan, R. E., Varady, K. A., Frasson, D., Hellerstein, M. K., Birkenfeld, A. L., Samuel, V. T., Shulman, G. I., Wang, Y., Kang, C. et al. 2009. Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity. Diabetes, 58(4):855-66.
Balagopal, P., Graham, T. E., Kahn, B. B., Altomare, A., Funanage, V., George, D. 2007. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. The Journal of clinical endocrinology and metabolism, 92(5):1971-4.
Bartz, R., Zehmer, J. K., Zhu, M., Chen, Y., Serrero, G., Zhao, Y., Liu, P. 2007. Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation. Journal of proteome research, 6(8):3256-65.
Bell, M., Wang, H., Chen, H., McLenithan, J. C., Gong, D. W., Yang, R. Z., Yu, D., Fried, S. K., Quon, M. J., Londos, C. et al. 2008. Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance. Diabetes, 57(8):2037-45.
Bezaire, V., Mairal, A., Ribet, C., Lefort, C., Girousse, A., Jocken, J., Laurencikiene, J., Anesia, R., Rodriguez, A. M., Ryden, M. et al. 2009. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. The Journal of biological chemistry, 284(27):18282-91.
Brunt, E. M., Janney, C. G., Di Bisceglie, A. M., Neuschwander-Tetri, B. A., Bacon, B. R. 1999.
Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. The American journal of gastroenterology, 94(9):2467-74.
Buchebner, M., Pfeifer, T., Rathke, N., Chandak, P. G., Lass, A., Schreiber, R., Kratzer, A., Zimmermann, R., Sattler, W., Koefeler, H. et al. 2010. Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363. Journal of lipid research, 51(10):2896-908.
Caldwell, S. H., Oelsner, D. H., Iezzoni, J. C., Hespenheide, E. E., Battle, E. H., Driscoll, C. J. 1999. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology, 29(3):664-9.
Chakrabarti, P., English, T., Shi, J., Smas, C. M., Kandror, K. V. 2010. Mammalian Target of Rapamycin Complex 1 Suppresses Lipolysis, Stimulates Lipogenesis, and Promotes Fat Storage. Diabetes, 59(4):775-781.
Chakrabarti, P., Kandror, K. V. 2009. FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes. The Journal of biological chemistry, 284(20):13296-300.
Chanarin, I., Patel, A., Slavin, G., Wills, E. J., Andrews, T. M., Stewart, G. 1975. Neutral-lipid storage disease: a new disorder of lipid metabolism. Br Med J, 1(5957):553-5.
Chen, W., Chang, B., Li, L., Chan, L. 2010. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology, 52(3):1134-42.
Chitturi, S., Wong, V. W.-S., Farrell, G. 2011. Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground. Journal of Gastroenterology and Hepatology, 26163-172.
Coderch, L., Lopez, O., de la Maza, A., Parra, J. L. 2003. Ceramides and skin function. American journal of clinical dermatology, 4(2):107-29.
Cortez-Pinto, H., Baptista, A., Camilo, M. E., De Moura, M. C. 2003. Nonalcoholic steatohepatitis--a long-term follow-up study: comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Digestive diseases and sciences, 48(10):1909-13.
Dam-Larsen, S., Franzmann, M., Andersen, I. B., Christoffersen, P., Jensen, L. B., Sorensen, T. I., Becker, U., Bendtsen, F. 2004. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut, 53(5):750-5.
DeLeve, L. D., Wang, X., Kanel, G. C., Atkinson, R. D., McCuskey, R. S. 2008. Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. Am J Pathol, 173(4):993-1001.
Demerjian, M., Crumrine, D. A., Milstone, L. M., Williams, M. L., Elias, P. M. 2006. Barrierdysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome). The Journal of investigative dermatology, 126(9):2032-8.
Donsmark, M., Langfort, J., Holm, C., Ploug, T., Galbo, H. 2004. Regulation and role of hormone-sensitive lipase in rat skeletal muscle. The Proceedings of the Nutrition Society, 63(2):309-14.
Donsmark, M., Langfort, J., Holm, C., Ploug, T., Galbo, H. 2005. Hormone-sensitive lipase as mediator of lipolysis in contracting skeletal muscle. Exercise and sport sciences reviews, 33(3):127-33.
Elias, P. M., Williams, M. L. 1985. Neutral lipid storage disease with ichthyosis. Defective lamellar body contents and intracellular dispersion. Archives of dermatology, 121(8):1000-8.
Elias, P. M., Williams, M. L., Holleran, W. M., Jiang, Y. J., Schmuth, M. 2008. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. Journal of lipid research, 49(4):697-714.
Escande, C., Chini, C. C., Nin, V., Dykhouse, K. M., Novak, C. M., Levine, J., van Deursen, J., Gores, G. J., Chen, J., Lou, Z. et al. 2010. Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice. J Clin Invest, 120(2):545-58.
Evans, R. M., Barish, G. D., Wang, Y. X. 2004. PPARs and the complex journey to obesity. Nature medicine, 10(4):355-61.
Falck-Ytter, Y., Younossi, Z. M., Marchesini, G., McCullough, A. J. 2001. Clinical features and natural history of nonalcoholic steatosis syndromes. Seminars in liver disease, 21(1):17-26.
Festuccia, W. T., Laplante, M., Berthiaume, M., Gelinas, Y., Deshaies, Y. 2006. PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control. Diabetologia, 49(10):2427-36.
Fischer, J., Lefevre, C., Morava, E., Mussini, J. M., Laforet, P., Negre-Salvayre, A., Lathrop, M., Salvayre, R. 2007. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nature genetics, 39(1):28-30.
Fortier, M., Soni, K., Laurin, N., Wang, S. P., Mauriege, P., Jirik, F. R., Mitchell, G. A. 2005.
Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice. Journal of lipid research, 46(9):1860-7.
Fortier, M., Wang, S. P., Mauriege, P., Semache, M., Mfuma, L., Li, H., Levy, E., Richard, D., Mitchell, G. A. 2004. Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading. American journal of physiology. Endocrinology and metabolism, 287(2):E282-8.
Fredrikson, G., Tornqvist, H., Belfrage, P. 1986. Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochimica et biophysica acta, 876(2):288-93.
Garton, A. J., Campbell, D. G., Carling, D., Hardie, D. G., Colbran, R. J., Yeaman, S. J. 1989.
Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism. European journal of biochemistry / FEBS, 179(1):249-54.
Gibbons, G. F., Islam, K., Pease, R. J. 2000. Mobilisation of triacylglycerol stores. Biochimica et biophysica acta, 1483(1):37-57. Graham, T. E., Yang, Q., Bluher, M., Hammarstedt, A., Ciaraldi, T. P., Henry, R. R., Wason, C. J., Oberbach, A., Jansson, P. A., Smith, U. et al. 2006. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. The New England journal of medicine, 354(24):2552-63.
Granneman, J. G., Moore, H. P., Granneman, R. L., Greenberg, A. S., Obin, M. S., Zhu, Z. 2007.
Analysis of lipolytic protein trafficking and interactions in adipocytes. The Journal of biological chemistry, 282(8):5726-35.
Granneman, J. G., Moore, H. P., Krishnamoorthy, R., Rathod, M. 2009. Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). The Journal of biological chemistry, 284(50):34538-44.
Gruber, A., Cornaciu, I., Lass, A., Schweiger, M., Poeschl, M., Eder, C., Kumari, M., Schoiswohl, G., Wolinski, H., Kohlwein, S. D. et al. 2010. The N-terminal Region of Comparative Gene Identification-58 (CGI-58) Is Important for Lipid Droplet Binding and Activation of Adipose Triglyceride Lipase. Journal of Biological Chemistry, 285(16):12289-12298.
Guo, Y., Walther, T. C., Rao, M., Stuurman, N., Goshima, G., Terayama, K., Wong, J. S., Vale, R. D., Walter, P., Farese, R. V. 2008. Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature, 453(7195):657-61.
Haemmerle, G., Lass, A., Zimmermann, R., Gorkiewicz, G., Meyer, C., Rozman, J., Heldmaier, G., Maier, R., Theussl, C., Eder, S. et al. 2006. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science, 312(5774):734-7.
Haemmerle, G., Zimmermann, R., Hayn, M., Theussl, C., Waeg, G., Wagner, E., Sattler, W., Magin, T. M., Wagner, E. F., Zechner, R. 2002. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem, 277(7):4806-15.
Hammarstedt, A., Pihlajamaki, J., Graham, T. E., Kainulainen, S., Kahn, B. B., Laakso, M., Smith, U. 2008. High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naive type 2 diabetic subjects. Journal of internal medicine, 263(4):440-9.
Hansson, O., Strom, K., Guner, N., Wierup, N., Sundler, F., Hoglund, P., Holm, C. 2006.
Inflammatory response in white adipose tissue in the non-obese hormone-sensitive lipase null mouse model. Journal of proteome research, 5(7):1701-10.
He, S., McPhaul, C., Li, J. Z., Garuti, R., Kinch, L., Grishin, N. V., Cohen, J. C., Hobbs, H. H. 2010. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. The Journal of biological chemistry, 285(9):6706-15.
Hebbard, L., George, J. 2011. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol, 8(1):35-44.
Hill-Baskin, A. E., Markiewski, M. M., Buchner, D. A., Shao, H., DeSantis, D., Hsiao, G., Subramaniam, S., Berger, N. A., Croniger, C., Lambris, J. D. et al. 2009. Diet-induced hepatocellular carcinoma in genetically predisposed mice. Hum Mol Genet, 18(16):2975-88.
Holm, C., Osterlund, T. 1999. Hormone-sensitive lipase and neutral cholesteryl ester lipase. Methods Mol Biol, 109109-21.
Hoy, A. J., Bruce, C. R., Turpin, S. M., Morris, A. J., Febbraio, M. A., Watt, M. J. 2011. Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation. Endocrinology, 152(1):48-58.
Hue, L., Taegtmeyer, H. 2009. The Randle cycle revisited: a new head for an old hat. American journal of physiology. Endocrinology and metabolism, 297(3):E578-91.
Huijsman, E., van de Par, C., Economou, C., van der Poel, C., Lynch, G. S., Schoiswohl, G., Haemmerle, G., Zechner, R., Watt, M. J. 2009. Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice. American journal of physiology. Endocrinology and metabolism, 297(2):E505-13.
Igal, R. A., Rhoads, J. M., Coleman, R. A. 1997. Neutral lipid storage disease with fatty liver and cholestasis. Journal of pediatric gastroenterology and nutrition, 25(5):541-7.
Ito, M., Suzuki, J., Tsujioka, S., Sasaki, M., Gomori, A., Shirakura, T., Hirose, H., Ishihara, A., Iwaasa, H., Kanatani, A. 2007. Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet. Hepatol Res, 37(1):50-7.
Jenkins, C. M., Mancuso, D. J., Yan, W., Sims, H. F., Gibson, B., Gross, R. W. 2004. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. The Journal of biological chemistry, 279(47):48968-75. Jiang, Y. J., Barish, G., Lu, B., Evans, R. M., Crumrine, D., Schmuth, M., Elias, P. M., Feingold, K.
R. 2010. PPARdelta activation promotes stratum corneum formation and epidermal permeability barrier development during late gestation. The Journal of investigative dermatology, 130(2):511-9.
Jiang, Y. J., Uchida, Y., Lu, B., Kim, P., Mao, C., Akiyama, M., Elias, P. M., Holleran, W. M., Grunfeld, C., Feingold, K. R. 2009. Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes. The Journal of biological chemistry, 284(28):18942-52.
Jocken, J. W., Langin, D., Smit, E., Saris, W. H., Valle, C., Hul, G. B., Holm, C., Arner, P., Blaak, E. E. 2007. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. The Journal of clinical endocrinology and metabolism, 92(6):2292-9.
Johnson, W. J., Jang, S. Y., Bernard, D. W. 2000. Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 126(4):543-52.
Jourdan, M., Jaleel, A., Karakelides, H., Ford, G. C., Kahn, B. B., Nair, K. S. 2009. Impact of type 1 diabetes and insulin treatment on plasma levels and fractional synthesis rate of retinol-binding protein 4. The Journal of clinical endocrinology and metabolism, 94(12):5125-30.
Kershaw, E. E., Hamm, J. K., Verhagen, L. A., Peroni, O., Katic, M., Flier, J. S. 2006. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes, 55(1):148-57.
Kershaw, E. E., Schupp, M., Guan, H. P., Gardner, N. P., Lazar, M. A., Flier, J. S. 2007.
PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. American journal of physiology. Endocrinology and metabolism, 293(6):E1736-45.
Kienesberger, P. C., Lee, D., Pulinilkunnil, T., Brenner, D. S., Cai, L., Magnes, C., Koefeler, H. C., Streith, I. E., Rechberger, G. N., Haemmerle, G. et al. 2009a. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. The Journal of biological chemistry, 284(44):30218-29.
Kienesberger, P. C., Lee, D., Pulinilkunnil, T., Brenner, D. S., Cai, L., Magnes, C., Koefeler, H. C., Streith, I. E., Rechberger, G. N., Haemmerle, G. et al. 2009b. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. The Journal of biological chemistry, 284(44):30218-29.
Kiens, B. 2006. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiological reviews, 86(1):205-43.
Kim, J. Y., Tillison, K., Lee, J. H., Rearick, D. A., Smas, C. M. 2006. The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma. American journal of physiology. Endocrinology and metabolism, 291(1):E115-27.
Kobayashi, K., Inoguchi, T., Maeda, Y., Nakashima, N., Kuwano, A., Eto, E., Ueno, N., Sasaki, S., Sawada, F., Fujii, M. et al. 2008. The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets. The Journal of clinical endocrinology and metabolism, 93(7):2877-84.
Kovacs, P., Geyer, M., Berndt, J., Kloting, N., Graham, T. E., Bottcher, Y., Enigk, B., Tonjes, A., Schleinitz, D., Schon, M. R. et al. 2007. Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression. Diabetes, 56(12):3095-100.
Kozlitina, J., Boerwinkle, E., Cohen, J. C., Hobbs, H. H. 2011. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology, 53(2):467-474.
Kraemer, F., Shen, W.-J. 2006. Hormone-Sensitive Lipase Knockouts. Nutrition & Metabolism, 3(1):12.
Kralisch, S., Klein, J., Lossner, U., Bluher, M., Paschke, R., Stumvoll, M., Fasshauer, M. 2005.
Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Molecular and cellular endocrinology, 240(1-2):43-9.
Krempler, F., Breban, D., Oberkofler, H., Esterbauer, H., Hell, E., Paulweber, B., Patsch, W. 2000.
Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors. Arterioscler Thromb Vasc Biol, 20(2):443-9.
Krintel, C., Osmark, P., Larsen, M. R., Resjo, S., Logan, D. T., Holm, C. 2008. Ser649 and Ser650 are the major determinants of protein kinase A-mediated activation of human hormone-sensitive lipase against lipid substrates. PloS one, 3(11):e3756.
Krzyzanowska, K., Zemany, L., Krugluger, W., Schernthaner, G. H., Mittermayer, F., Schnack, C., Rahman, R., Brix, J., Kahn, B. B., Schernthaner, G. 2008. Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes. Diabetologia, 51(7):1115-22.
Langin, D., Dicker, A., Tavernier, G., Hoffstedt, J., Mairal, A., Ryden, M., Arner, E., Sicard, A., Jenkins, C. M., Viguerie, N. et al. 2005. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes, 54(11):3190-7.
Larter, C. Z., Yeh, M. M. 2008. Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol, 23(11):1635-48.
Lass, A., Zimmermann, R., Haemmerle, G., Riederer, M., Schoiswohl, G., Schweiger, M., Kienesberger, P., Strauss, J. G., Gorkiewicz, G., Zechner, R. 2006. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab, 3(5):309-19.
Lass, A., Zimmermann, R., Oberer, M., Zechner, R. 2011. Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Progress in lipid research, 50(1):14-27.
Lee, S. J., Heinrich, G., Fedorova, L., Al-Share, Q. Y., Ledford, K. J., Fernstrom, M. A., McInerney, M. F., Erickson, S. K., Gatto-Weis, C., Najjar, S. M. 2008. Development of nonalcoholic steatohepatitis in insulin-resistant liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant mice. Gastroenterology, 135(6):2084-95.
Lefevre, C., Jobard, F., Caux, F., Bouadjar, B., Karaduman, A., Heilig, R., Lakhdar, H., Wollenberg,
A., Verret, J. L., Weissenbach, J. et al. 2001. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. American journal of human genetics, 69(5):1002-12.
Lefkowitch, J. H. 2005. Morphology of alcoholic liver disease. Clinics in liver disease, 9(1):37-53.
Lelliott, C., Vidal-Puig, A. J. 2004. Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation. Int J Obes Relat Metab Disord, 28 Suppl 4S22-8.
Li, Y., Xu, C., Yu, C., Xu, L., Miao, M. 2009. Association of serum uric acid level with non-alcoholic fatty liver disease: a cross-sectional study. Journal of hepatology, 50(5):1029-34.
Liu, L. F., Purushotham, A., Wendel, A. A., Koba, K., DeIuliis, J., Lee, K., Belury, M. A. 2009.
Regulation of adipose triglyceride lipase by rosiglitazone. Diabetes, obesity & metabolism, 11(2):131-42.
Loguercio, C., De Girolamo, V., de Sio, I., Tuccillo, C., Ascione, A., Baldi, F., Budillon, G., Cimino, L., Di Carlo, A., Di Marino, M. P. et al. 2001. Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects. Journal of hepatology, 35(5):568-74.
Loguercio, C., De Simone, T., D'Auria, M. V., de Sio, I., Federico, A., Tuccillo, C., Abbatecola, A. M., Del Vecchio Blanco, C. 2004. Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 36(6):398-405.
Ludwig, J., Viggiano, T. R., McGill, D. B., Oh, B. J. 1980. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic proceedings. Mayo Clinic, 55(7):434-8.
Man, M. Q., Barish, G. D., Schmuth, M., Crumrine, D., Barak, Y., Chang, S., Jiang, Y., Evans, R. M., Elias, P. M., Feingold, K. R. 2008. Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation. The Journal of investigative dermatology, 128(2):370-7.
Mannaerts, G. P., Debeer, L. J., Thomas, J., De Schepper, P. J. 1979. Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates and isolated hepatocytes from control and clofibrate-treated rats. The Journal of biological chemistry, 254(11):4585-95.
Martinez-Botas, J., Anderson, J. B., Tessier, D., Lapillonne, A., Chang, B. H., Quast, M. J., Gorenstein, D., Chen, K. H., Chan, L. 2000. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nature genetics, 26(4):474-9.
Martinez-Clemente, M., Ferre, N., Gonzalez-Periz, A., Lopez-Parra, M., Horrillo, R., Titos, E., Moran-Salvador, E., Miquel, R., Arroyo, V., Funk, C. D. et al. 2010. 5-lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor alpha-induced hepatocyte damage in hyperlipidemia-prone ApoE-null mice. Hepatology, 51(3):817-27.
Matteoni, C. A., Younossi, Z. M., Gramlich, T., Boparai, N., Liu, Y. C., McCullough, A. J. 1999.
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology, 116(6):1413-9.
McGarry, J. D., Mannaerts, G. P., Foster, D. W. 1977. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest, 60(1):265-70.
Mello, T., Nakatsuka, A., Fears, S., Davis, W., Tsukamoto, H., Bosron, W. F., Sanghani, S. P. 2008.
Expression of carboxylesterase and lipase genes in rat liver cell-types. Biochemical and biophysical research communications, 374(3):460-464.
Miyoshi, H., Perfield, J. W., 2nd, Souza, S. C., Shen, W. J., Zhang, H. H., Stancheva, Z. S., Kraemer, F. B., Obin, M. S., Greenberg, A. S. 2007. Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes. The Journal of biological chemistry, 282(2):996-1002.
Mizutani, Y., Mitsutake, S., Tsuji, K., Kihara, A., Igarashi, Y. 2009. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie, 91(6):784-90.
Monetti, M., Levin, M. C., Watt, M. J., Sajan, M. P., Marmor, S., Hubbard, B. K., Stevens, R. D., Bain, J. R., Newgard, C. B., Farese, R. V., Sr. et al. 2007. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab, 6(1):69-78.
Neuschwander-Tetri, B. A., Bacon, B. R. 1996. Nonalcoholic steatohepatitis. The Medical clinics of North America, 80(5):1147-66.
Notari, L., Baladron, V., Aroca-Aguilar, J. D., Balko, N., Heredia, R., Meyer, C., Notario, P. M., Saravanamuthu, S., Nueda, M. L., Sanchez-Sanchez, F. et al. 2006. Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. The Journal of biological chemistry,281(49):38022-37.
Olivecrona, G. 2010. The crucial role of ATGL for energy supply of muscles. Journal of lipid research, 51(3):449-50.
Olsson, H., Stralfors, P., Belfrage, P. 1986. Phosphorylation of the basal site of hormone-sensitive lipase by glycogen synthase kinase-4. FEBS letters, 209(2):175-80.
Ong, K. T., Mashek, M. T., Bu, S. Y., Greenberg, A. S., Mashek, D. G. 2010. Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning. Hepatology.
Osei-Hyiaman, D., Liu, J., Zhou, L., Godlewski, G., Harvey-White, J., Jeong, W. I., Batkai, S., Marsicano, G., Lutz, B., Buettner, C. et al. 2008. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest, 118(9):3160-9.
Peyot, M. L., Guay, C., Latour, M. G., Lamontagne, J., Lussier, R., Pineda, M., Ruderman, N. B., Haemmerle, G., Zechner, R., Joly, E. et al. 2009. Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion. The Journal of biological chemistry, 284(25):16848-59.
Ploeg, R. J., D'Alessandro, A. M., Knechtle, S. J., Stegall, M. D., Pirsch, J. D., Hoffmann, R. M., Sasaki, T., Sollinger, H. W., Belzer, F. O., Kalayoglu, M. 1993. Risk factors for primary dysfunction after liver transplantation--a multivariate analysis. Transplantation, 55(4):807-13.
Purushotham, A., Schug, T. T., Xu, Q., Surapureddi, S., Guo, X., Li, X. 2009. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab, 9(4):327-38.
Radner, F. P., Streith, I. E., Schoiswohl, G., Schweiger, M., Kumari, M., Eichmann, T. O., Rechberger, G., Koefeler, H. C., Eder, S., Schauer, S. et al. 2010. Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58). The Journal of biological chemistry, 285(10):7300-11.
Randle, P. J., Garland, P. B., Hales, C. N., Newsholme, E. A. 1963. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 1(7285):785-9.
Roduit, R., Masiello, P., Wang, S. P., Li, H., Mitchell, G. A., Prentki, M. 2001. A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice. Diabetes, 50(9):1970-5.
Rogalska, E., Cudrey, C., Ferrato, F., Verger, R. 1993. Stereoselective hydrolysis of triglycerides by animal and microbial lipases. Chirality, 5(1):24-30.
Russell, L., Forsdyke, D. R. 1991. A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated. DNA Cell Biol, 10(8):581-91.
Rydel, T. J., Williams, J. M., Krieger, E., Moshiri, F., Stallings, W. C., Brown, S. M., Pershing, J. C., Purcell, J. P., Alibhai, M. F. 2003. The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a Ser-Asp catalytic dyad. Biochemistry, 42(22):6696-708.
Schaffer, J. E. 2003. Lipotoxicity: when tissues overeat. Current opinion in lipidology, 14(3):281-7.
Schlosburg, J. E., Blankman, J. L., Long, J. Z., Nomura, D. K., Pan, B., Kinsey, S. G., Nguyen, P. T., Ramesh, D., Booker, L., Burston, J. J. et al. 2010. Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci, 13(9):1113-9.
Schoiswohl, G., Schweiger, M., Schreiber, R., Gorkiewicz, G., Preiss-Landl, K., Taschler, U., Zierler, K. A., Radner, F. P., Eichmann, T. O., Kienesberger, P. C. et al. 2010. Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids. Journal of lipid research, 51(3):490-9.
Schweiger, M., Lass, A., Zimmermann, R., Eichmann, T. O., Zechner, R. 2009. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. American journal of physiology. Endocrinology and metabolism, 297(2):E289-96.
Schweiger, M., Schoiswohl, G., Lass, A., Radner, F. P., Haemmerle, G., Malli, R., Graier, W., Cornaciu, I., Oberer, M., Salvayre, R. et al. 2008. The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding. The Journal of biological chemistry, 283(25):17211-20.
Schweiger, M., Schreiber, R., Haemmerle, G., Lass, A., Fledelius, C., Jacobsen, P., Tornqvist, H., Zechner, R., Zimmermann, R. 2006. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. The Journal of biological chemistry, 281(52):40236-41.
Schwimmer, J. B., Behling, C., Newbury, R., Deutsch, R., Nievergelt, C., Schork, N. J., Lavine, J. E. 2005. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology, 42(3):641-9.
Sheriff, S., Du, H., Grabowski, G. A. 1995. Characterization of lysosomal acid lipase by site-directed mutagenesis and heterologous expression. J Biol Chem, 270(46):27766-72.
Shewry, P. R. 2003. Tuber storage proteins. Ann Bot, 91(7):755-69.
Silverman, J. F., O'Brien, K. F., Long, S., Leggett, N., Khazanie, P. G., Pories, W. J., Norris, H. T., Caro, J. F. 1990. Liver pathology in morbidly obese patients with and without diabetes. The American journal of gastroenterology, 85(10):1349-55.
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., Czaja, M. J. 2009a. Autophagy regulates lipid metabolism. Nature, 458(7242):1131-5.
Singh, R., Wang, Y., Xiang, Y., Tanaka, K. E., Gaarde, W. A., Czaja, M. J. 2009b. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology, 49(1):87-96.
Sirois, J., Cote, J. F., Charest, A., Uetani, N., Bourdeau, A., Duncan, S. A., Daniels, E., Tremblay, M. L. 2006. Essential function of PTP-PEST during mouse embryonic vascularization, mesenchyme formation, neurogenesis and early liver development. Mech Dev, 123(12):869-80.
Slawik, M., Vidal-Puig, A. J. 2006. Lipotoxicity, overnutrition and energy metabolism in aging. Ageing Res Rev, 5(2):144-64.
Soni, K. G., Mardones, G. A., Sougrat, R., Smirnova, E., Jackson, C. L., Bonifacino, J. S. 2009a.
Coatomer-dependent protein delivery to lipid droplets. Journal of cell science, 122(Pt 11):1834-41.
Soni, K. G., Mardones, G. A., Sougrat, R., Smirnova, E., Jackson, C. L., Bonifacino, J. S. 2009b.
Coatomer-dependent protein delivery to lipid droplets. Journal of cell science, 122(Pt 11):1834-41.
Stumptner, C., Fuchsbichler, A., Heid, H., Zatloukal, K., Denk, H. 2002. Mallory body--a disease-associated type of sequestosome. Hepatology, 35(5):1053-62.
Subramanian, V., Rothenberg, A., Gomez, C., Cohen, A. W., Garcia, A., Bhattacharyya, S., Shapiro, L., Dolios, G., Wang, R., Lisanti, M. P. et al. 2004. Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes. The Journal of biological chemistry, 279(40):42062-71.
Sztalryd, C., Xu, G., Dorward, H., Tansey, J. T., Contreras, J. A., Kimmel, A. R., Londos, C. 2003.
Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation. The Journal of cell biology, 161(6):1093-103.
Tang, J., Kriz, R. W., Wolfman, N., Shaffer, M., Seehra, J., Jones, S. S. 1997. A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs. The Journal of biological chemistry, 272(13):8567-75.
Tansey, J. T., Huml, A. M., Vogt, R., Davis, K. E., Jones, J. M., Fraser, K. A., Brasaemle, D. L., Kimmel, A. R., Londos, C. 2003. Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols. The Journal of biological chemistry, 278(10):8401-6.
Taschler, U., Radner, F. P., Heier, C., Schreiber, R., Schweiger, M., Schoiswohl, G., Preiss-Landl, K., Jaeger, D., Reiter, B., Koefeler, H. C. et al. 2011. Monoglyceride lipase-deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. The Journal of biological chemistry.
Tiniakos, D. G., Vos, M. B., Brunt, E. M. 2010. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annual review of pathology, 5145-71.
van Kempen, A. A., van der Crabben, S. N., Ackermans, M. T., Endert, E., Kok, J. H., Sauerwein, H. P. 2006. Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile. Am J Physiol Endocrinol Metab, 290(4):E723-30.
Villena, J. A., Roy, S., Sarkadi-Nagy, E., Kim, K. H., Sul, H. S. 2004. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. The Journal of biological chemistry, 279(45):47066-75.
Wang, H., Hu, L., Dalen, K., Dorward, H., Marcinkiewicz, A., Russell, D., Gong, D., Londos, C., Yamaguchi, T., Holm, C. et al. 2009. Activation of hormone-sensitive lipase requires two steps, protein phosphorylation and binding to the PAT-1 domain of lipid droplet coat proteins. The Journal of biological chemistry, 284(46):32116-25.
Wang, S. P., Laurin, N., Himms-Hagen, J., Rudnicki, M. A., Levy, E., Robert, M. F., Pan, L., Oligny, L., Mitchell, G. A. 2001. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes Res, 9(2):119-28.
Wang, S. P., Marth, J. D., Oligny, L. L., Vachon, M., Robert, M. F., Ashmarina, L., Mitchell, G. A. 1998. 3-Hydroxy-3-methylglutaryl-CoA lyase (HL): gene targeting causes prenatal lethality inHL-deficient mice. Hum Mol Genet, 7(13):2057-62.
Watt, M. J., Spriet, L. L. 2004. Regulation and role of hormone-sensitive lipase activity in human skeletal muscle. The Proceedings of the Nutrition Society, 63(2):315-22.
Wei, E., Ben Ali, Y., Lyon, J., Wang, H., Nelson, R., Dolinsky, V. W., Dyck, J. R., Mitchell, G., Korbutt, G. S., Lehner, R. 2010. Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure. Cell Metab, 11(3):183-93.
Wu, Q., Ortegon, A. M., Tsang, B., Doege, H., Feingold, K. R., Stahl, A. 2006. FATP1 is an insulin-sensitive fatty acid transporter involved in diet-induced obesity. Mol Cell Biol, 26(9):3455-67.
Yang, Q., Graham, T. E., Mody, N., Preitner, F., Peroni, O. D., Zabolotny, J. M., Kotani, K., Quadro, L., Kahn, B. B. 2005. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436(7049):356-62.
Yang, X., Lu, X., Lombes, M., Rha, G. B., Chi, Y. I., Guerin, T. M., Smart, E. J., Liu, J. 2010. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab, 11(3):194-205.
Yeaman, S. J. 2004. Hormone-sensitive lipase--new roles for an old enzyme. The Biochemical journal, 379(Pt 1):11-22.
Zafrani, E. S. 2004. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Archiv : an international journal of pathology, 444(1):3-12.
Zimmermann, R., Strauss, J. G., Haemmerle, G., Schoiswohl, G., Birner-Gruenberger, R., Riederer, M., Lass, A., Neuberger, G., Eisenhaber, F., Hermetter, A. et al. 2004. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science, 306(5700):1383-6.
Ahmadian, M., Duncan, R. E., Varady, K. A., Frasson, D., Hellerstein, M. K., Birkenfeld, A. L., Samuel, V. T., Shulman, G. I., Wang, Y., Kang, C. et al. 2009. Adipose overexpression of desnutrin promotes fatty acid use and attenuates diet-induced obesity. Diabetes, 58(4):855-66.
Balagopal, P., Graham, T. E., Kahn, B. B., Altomare, A., Funanage, V., George, D. 2007. Reduction of elevated serum retinol binding protein in obese children by lifestyle intervention: association with subclinical inflammation. The Journal of clinical endocrinology and metabolism, 92(5):1971-4.
Bartz, R., Zehmer, J. K., Zhu, M., Chen, Y., Serrero, G., Zhao, Y., Liu, P. 2007. Dynamic activity of lipid droplets: protein phosphorylation and GTP-mediated protein translocation. Journal of proteome research, 6(8):3256-65.
Bell, M., Wang, H., Chen, H., McLenithan, J. C., Gong, D. W., Yang, R. Z., Yu, D., Fried, S. K., Quon, M. J., Londos, C. et al. 2008. Consequences of lipid droplet coat protein downregulation in liver cells: abnormal lipid droplet metabolism and induction of insulin resistance. Diabetes, 57(8):2037-45.
Bezaire, V., Mairal, A., Ribet, C., Lefort, C., Girousse, A., Jocken, J., Laurencikiene, J., Anesia, R., Rodriguez, A. M., Ryden, M. et al. 2009. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes. The Journal of biological chemistry, 284(27):18282-91.
Brunt, E. M., Janney, C. G., Di Bisceglie, A. M., Neuschwander-Tetri, B. A., Bacon, B. R. 1999.
Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. The American journal of gastroenterology, 94(9):2467-74.
Buchebner, M., Pfeifer, T., Rathke, N., Chandak, P. G., Lass, A., Schreiber, R., Kratzer, A., Zimmermann, R., Sattler, W., Koefeler, H. et al. 2010. Cholesteryl ester hydrolase activity is abolished in HSL-/- macrophages but unchanged in macrophages lacking KIAA1363. Journal of lipid research, 51(10):2896-908.
Caldwell, S. H., Oelsner, D. H., Iezzoni, J. C., Hespenheide, E. E., Battle, E. H., Driscoll, C. J. 1999. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology, 29(3):664-9.
Chakrabarti, P., English, T., Shi, J., Smas, C. M., Kandror, K. V. 2010. Mammalian Target of Rapamycin Complex 1 Suppresses Lipolysis, Stimulates Lipogenesis, and Promotes Fat Storage. Diabetes, 59(4):775-781.
Chakrabarti, P., Kandror, K. V. 2009. FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes. The Journal of biological chemistry, 284(20):13296-300.
Chanarin, I., Patel, A., Slavin, G., Wills, E. J., Andrews, T. M., Stewart, G. 1975. Neutral-lipid storage disease: a new disorder of lipid metabolism. Br Med J, 1(5957):553-5.
Chen, W., Chang, B., Li, L., Chan, L. 2010. Patatin-like phospholipase domain-containing 3/adiponutrin deficiency in mice is not associated with fatty liver disease. Hepatology, 52(3):1134-42.
Chitturi, S., Wong, V. W.-S., Farrell, G. 2011. Nonalcoholic fatty liver in Asia: Firmly entrenched and rapidly gaining ground. Journal of Gastroenterology and Hepatology, 26163-172.
Coderch, L., Lopez, O., de la Maza, A., Parra, J. L. 2003. Ceramides and skin function. American journal of clinical dermatology, 4(2):107-29.
Cortez-Pinto, H., Baptista, A., Camilo, M. E., De Moura, M. C. 2003. Nonalcoholic steatohepatitis--a long-term follow-up study: comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Digestive diseases and sciences, 48(10):1909-13.
Dam-Larsen, S., Franzmann, M., Andersen, I. B., Christoffersen, P., Jensen, L. B., Sorensen, T. I., Becker, U., Bendtsen, F. 2004. Long term prognosis of fatty liver: risk of chronic liver disease and death. Gut, 53(5):750-5.
DeLeve, L. D., Wang, X., Kanel, G. C., Atkinson, R. D., McCuskey, R. S. 2008. Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. Am J Pathol, 173(4):993-1001.
Demerjian, M., Crumrine, D. A., Milstone, L. M., Williams, M. L., Elias, P. M. 2006. Barrierdysfunction and pathogenesis of neutral lipid storage disease with ichthyosis (Chanarin-Dorfman syndrome). The Journal of investigative dermatology, 126(9):2032-8.
Donsmark, M., Langfort, J., Holm, C., Ploug, T., Galbo, H. 2004. Regulation and role of hormone-sensitive lipase in rat skeletal muscle. The Proceedings of the Nutrition Society, 63(2):309-14.
Donsmark, M., Langfort, J., Holm, C., Ploug, T., Galbo, H. 2005. Hormone-sensitive lipase as mediator of lipolysis in contracting skeletal muscle. Exercise and sport sciences reviews, 33(3):127-33.
Elias, P. M., Williams, M. L. 1985. Neutral lipid storage disease with ichthyosis. Defective lamellar body contents and intracellular dispersion. Archives of dermatology, 121(8):1000-8.
Elias, P. M., Williams, M. L., Holleran, W. M., Jiang, Y. J., Schmuth, M. 2008. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism. Journal of lipid research, 49(4):697-714.
Escande, C., Chini, C. C., Nin, V., Dykhouse, K. M., Novak, C. M., Levine, J., van Deursen, J., Gores, G. J., Chen, J., Lou, Z. et al. 2010. Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice. J Clin Invest, 120(2):545-58.
Evans, R. M., Barish, G. D., Wang, Y. X. 2004. PPARs and the complex journey to obesity. Nature medicine, 10(4):355-61.
Falck-Ytter, Y., Younossi, Z. M., Marchesini, G., McCullough, A. J. 2001. Clinical features and natural history of nonalcoholic steatosis syndromes. Seminars in liver disease, 21(1):17-26.
Festuccia, W. T., Laplante, M., Berthiaume, M., Gelinas, Y., Deshaies, Y. 2006. PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control. Diabetologia, 49(10):2427-36.
Fischer, J., Lefevre, C., Morava, E., Mussini, J. M., Laforet, P., Negre-Salvayre, A., Lathrop, M., Salvayre, R. 2007. The gene encoding adipose triglyceride lipase (PNPLA2) is mutated in neutral lipid storage disease with myopathy. Nature genetics, 39(1):28-30.
Fortier, M., Soni, K., Laurin, N., Wang, S. P., Mauriege, P., Jirik, F. R., Mitchell, G. A. 2005.
Human hormone-sensitive lipase (HSL): expression in white fat corrects the white adipose phenotype of HSL-deficient mice. Journal of lipid research, 46(9):1860-7.
Fortier, M., Wang, S. P., Mauriege, P., Semache, M., Mfuma, L., Li, H., Levy, E., Richard, D., Mitchell, G. A. 2004. Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading. American journal of physiology. Endocrinology and metabolism, 287(2):E282-8.
Fredrikson, G., Tornqvist, H., Belfrage, P. 1986. Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochimica et biophysica acta, 876(2):288-93.
Garton, A. J., Campbell, D. G., Carling, D., Hardie, D. G., Colbran, R. J., Yeaman, S. J. 1989.
Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein kinase. A possible antilipolytic mechanism. European journal of biochemistry / FEBS, 179(1):249-54.
Gibbons, G. F., Islam, K., Pease, R. J. 2000. Mobilisation of triacylglycerol stores. Biochimica et biophysica acta, 1483(1):37-57. Graham, T. E., Yang, Q., Bluher, M., Hammarstedt, A., Ciaraldi, T. P., Henry, R. R., Wason, C. J., Oberbach, A., Jansson, P. A., Smith, U. et al. 2006. Retinol-binding protein 4 and insulin resistance in lean, obese, and diabetic subjects. The New England journal of medicine, 354(24):2552-63.
Granneman, J. G., Moore, H. P., Granneman, R. L., Greenberg, A. S., Obin, M. S., Zhu, Z. 2007.
Analysis of lipolytic protein trafficking and interactions in adipocytes. The Journal of biological chemistry, 282(8):5726-35.
Granneman, J. G., Moore, H. P., Krishnamoorthy, R., Rathod, M. 2009. Perilipin controls lipolysis by regulating the interactions of AB-hydrolase containing 5 (Abhd5) and adipose triglyceride lipase (Atgl). The Journal of biological chemistry, 284(50):34538-44.
Gruber, A., Cornaciu, I., Lass, A., Schweiger, M., Poeschl, M., Eder, C., Kumari, M., Schoiswohl, G., Wolinski, H., Kohlwein, S. D. et al. 2010. The N-terminal Region of Comparative Gene Identification-58 (CGI-58) Is Important for Lipid Droplet Binding and Activation of Adipose Triglyceride Lipase. Journal of Biological Chemistry, 285(16):12289-12298.
Guo, Y., Walther, T. C., Rao, M., Stuurman, N., Goshima, G., Terayama, K., Wong, J. S., Vale, R. D., Walter, P., Farese, R. V. 2008. Functional genomic screen reveals genes involved in lipid-droplet formation and utilization. Nature, 453(7195):657-61.
Haemmerle, G., Lass, A., Zimmermann, R., Gorkiewicz, G., Meyer, C., Rozman, J., Heldmaier, G., Maier, R., Theussl, C., Eder, S. et al. 2006. Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase. Science, 312(5774):734-7.
Haemmerle, G., Zimmermann, R., Hayn, M., Theussl, C., Waeg, G., Wagner, E., Sattler, W., Magin, T. M., Wagner, E. F., Zechner, R. 2002. Hormone-sensitive lipase deficiency in mice causes diglyceride accumulation in adipose tissue, muscle, and testis. J Biol Chem, 277(7):4806-15.
Hammarstedt, A., Pihlajamaki, J., Graham, T. E., Kainulainen, S., Kahn, B. B., Laakso, M., Smith, U. 2008. High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naive type 2 diabetic subjects. Journal of internal medicine, 263(4):440-9.
Hansson, O., Strom, K., Guner, N., Wierup, N., Sundler, F., Hoglund, P., Holm, C. 2006.
Inflammatory response in white adipose tissue in the non-obese hormone-sensitive lipase null mouse model. Journal of proteome research, 5(7):1701-10.
He, S., McPhaul, C., Li, J. Z., Garuti, R., Kinch, L., Grishin, N. V., Cohen, J. C., Hobbs, H. H. 2010. A sequence variation (I148M) in PNPLA3 associated with nonalcoholic fatty liver disease disrupts triglyceride hydrolysis. The Journal of biological chemistry, 285(9):6706-15.
Hebbard, L., George, J. 2011. Animal models of nonalcoholic fatty liver disease. Nat Rev Gastroenterol Hepatol, 8(1):35-44.
Hill-Baskin, A. E., Markiewski, M. M., Buchner, D. A., Shao, H., DeSantis, D., Hsiao, G., Subramaniam, S., Berger, N. A., Croniger, C., Lambris, J. D. et al. 2009. Diet-induced hepatocellular carcinoma in genetically predisposed mice. Hum Mol Genet, 18(16):2975-88.
Holm, C., Osterlund, T. 1999. Hormone-sensitive lipase and neutral cholesteryl ester lipase. Methods Mol Biol, 109109-21.
Hoy, A. J., Bruce, C. R., Turpin, S. M., Morris, A. J., Febbraio, M. A., Watt, M. J. 2011. Adipose triglyceride lipase-null mice are resistant to high-fat diet-induced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation. Endocrinology, 152(1):48-58.
Hue, L., Taegtmeyer, H. 2009. The Randle cycle revisited: a new head for an old hat. American journal of physiology. Endocrinology and metabolism, 297(3):E578-91.
Huijsman, E., van de Par, C., Economou, C., van der Poel, C., Lynch, G. S., Schoiswohl, G., Haemmerle, G., Zechner, R., Watt, M. J. 2009. Adipose triacylglycerol lipase deletion alters whole body energy metabolism and impairs exercise performance in mice. American journal of physiology. Endocrinology and metabolism, 297(2):E505-13.
Igal, R. A., Rhoads, J. M., Coleman, R. A. 1997. Neutral lipid storage disease with fatty liver and cholestasis. Journal of pediatric gastroenterology and nutrition, 25(5):541-7.
Ito, M., Suzuki, J., Tsujioka, S., Sasaki, M., Gomori, A., Shirakura, T., Hirose, H., Ishihara, A., Iwaasa, H., Kanatani, A. 2007. Longitudinal analysis of murine steatohepatitis model induced by chronic exposure to high-fat diet. Hepatol Res, 37(1):50-7.
Jenkins, C. M., Mancuso, D. J., Yan, W., Sims, H. F., Gibson, B., Gross, R. W. 2004. Identification, cloning, expression, and purification of three novel human calcium-independent phospholipase A2 family members possessing triacylglycerol lipase and acylglycerol transacylase activities. The Journal of biological chemistry, 279(47):48968-75. Jiang, Y. J., Barish, G., Lu, B., Evans, R. M., Crumrine, D., Schmuth, M., Elias, P. M., Feingold, K.
R. 2010. PPARdelta activation promotes stratum corneum formation and epidermal permeability barrier development during late gestation. The Journal of investigative dermatology, 130(2):511-9.
Jiang, Y. J., Uchida, Y., Lu, B., Kim, P., Mao, C., Akiyama, M., Elias, P. M., Holleran, W. M., Grunfeld, C., Feingold, K. R. 2009. Ceramide stimulates ABCA12 expression via peroxisome proliferator-activated receptor {delta} in human keratinocytes. The Journal of biological chemistry, 284(28):18942-52.
Jocken, J. W., Langin, D., Smit, E., Saris, W. H., Valle, C., Hul, G. B., Holm, C., Arner, P., Blaak, E. E. 2007. Adipose triglyceride lipase and hormone-sensitive lipase protein expression is decreased in the obese insulin-resistant state. The Journal of clinical endocrinology and metabolism, 92(6):2292-9.
Johnson, W. J., Jang, S. Y., Bernard, D. W. 2000. Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 126(4):543-52.
Jourdan, M., Jaleel, A., Karakelides, H., Ford, G. C., Kahn, B. B., Nair, K. S. 2009. Impact of type 1 diabetes and insulin treatment on plasma levels and fractional synthesis rate of retinol-binding protein 4. The Journal of clinical endocrinology and metabolism, 94(12):5125-30.
Kershaw, E. E., Hamm, J. K., Verhagen, L. A., Peroni, O., Katic, M., Flier, J. S. 2006. Adipose triglyceride lipase: function, regulation by insulin, and comparison with adiponutrin. Diabetes, 55(1):148-57.
Kershaw, E. E., Schupp, M., Guan, H. P., Gardner, N. P., Lazar, M. A., Flier, J. S. 2007.
PPARgamma regulates adipose triglyceride lipase in adipocytes in vitro and in vivo. American journal of physiology. Endocrinology and metabolism, 293(6):E1736-45.
Kienesberger, P. C., Lee, D., Pulinilkunnil, T., Brenner, D. S., Cai, L., Magnes, C., Koefeler, H. C., Streith, I. E., Rechberger, G. N., Haemmerle, G. et al. 2009a. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. The Journal of biological chemistry, 284(44):30218-29.
Kienesberger, P. C., Lee, D., Pulinilkunnil, T., Brenner, D. S., Cai, L., Magnes, C., Koefeler, H. C., Streith, I. E., Rechberger, G. N., Haemmerle, G. et al. 2009b. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. The Journal of biological chemistry, 284(44):30218-29.
Kiens, B. 2006. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiological reviews, 86(1):205-43.
Kim, J. Y., Tillison, K., Lee, J. H., Rearick, D. A., Smas, C. M. 2006. The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-alpha in 3T3-L1 adipocytes and is a target for transactivation by PPARgamma. American journal of physiology. Endocrinology and metabolism, 291(1):E115-27.
Kobayashi, K., Inoguchi, T., Maeda, Y., Nakashima, N., Kuwano, A., Eto, E., Ueno, N., Sasaki, S., Sawada, F., Fujii, M. et al. 2008. The lack of the C-terminal domain of adipose triglyceride lipase causes neutral lipid storage disease through impaired interactions with lipid droplets. The Journal of clinical endocrinology and metabolism, 93(7):2877-84.
Kovacs, P., Geyer, M., Berndt, J., Kloting, N., Graham, T. E., Bottcher, Y., Enigk, B., Tonjes, A., Schleinitz, D., Schon, M. R. et al. 2007. Effects of genetic variation in the human retinol binding protein-4 gene (RBP4) on insulin resistance and fat depot-specific mRNA expression. Diabetes, 56(12):3095-100.
Kozlitina, J., Boerwinkle, E., Cohen, J. C., Hobbs, H. H. 2011. Dissociation between APOC3 variants, hepatic triglyceride content and insulin resistance. Hepatology, 53(2):467-474.
Kraemer, F., Shen, W.-J. 2006. Hormone-Sensitive Lipase Knockouts. Nutrition & Metabolism, 3(1):12.
Kralisch, S., Klein, J., Lossner, U., Bluher, M., Paschke, R., Stumvoll, M., Fasshauer, M. 2005.
Isoproterenol, TNFalpha, and insulin downregulate adipose triglyceride lipase in 3T3-L1 adipocytes. Molecular and cellular endocrinology, 240(1-2):43-9.
Krempler, F., Breban, D., Oberkofler, H., Esterbauer, H., Hell, E., Paulweber, B., Patsch, W. 2000.
Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors. Arterioscler Thromb Vasc Biol, 20(2):443-9.
Krintel, C., Osmark, P., Larsen, M. R., Resjo, S., Logan, D. T., Holm, C. 2008. Ser649 and Ser650 are the major determinants of protein kinase A-mediated activation of human hormone-sensitive lipase against lipid substrates. PloS one, 3(11):e3756.
Krzyzanowska, K., Zemany, L., Krugluger, W., Schernthaner, G. H., Mittermayer, F., Schnack, C., Rahman, R., Brix, J., Kahn, B. B., Schernthaner, G. 2008. Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes. Diabetologia, 51(7):1115-22.
Langin, D., Dicker, A., Tavernier, G., Hoffstedt, J., Mairal, A., Ryden, M., Arner, E., Sicard, A., Jenkins, C. M., Viguerie, N. et al. 2005. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes, 54(11):3190-7.
Larter, C. Z., Yeh, M. M. 2008. Animal models of NASH: getting both pathology and metabolic context right. J Gastroenterol Hepatol, 23(11):1635-48.
Lass, A., Zimmermann, R., Haemmerle, G., Riederer, M., Schoiswohl, G., Schweiger, M., Kienesberger, P., Strauss, J. G., Gorkiewicz, G., Zechner, R. 2006. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome. Cell Metab, 3(5):309-19.
Lass, A., Zimmermann, R., Oberer, M., Zechner, R. 2011. Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores. Progress in lipid research, 50(1):14-27.
Lee, S. J., Heinrich, G., Fedorova, L., Al-Share, Q. Y., Ledford, K. J., Fernstrom, M. A., McInerney, M. F., Erickson, S. K., Gatto-Weis, C., Najjar, S. M. 2008. Development of nonalcoholic steatohepatitis in insulin-resistant liver-specific S503A carcinoembryonic antigen-related cell adhesion molecule 1 mutant mice. Gastroenterology, 135(6):2084-95.
Lefevre, C., Jobard, F., Caux, F., Bouadjar, B., Karaduman, A., Heilig, R., Lakhdar, H., Wollenberg,
A., Verret, J. L., Weissenbach, J. et al. 2001. Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome. American journal of human genetics, 69(5):1002-12.
Lefkowitch, J. H. 2005. Morphology of alcoholic liver disease. Clinics in liver disease, 9(1):37-53.
Lelliott, C., Vidal-Puig, A. J. 2004. Lipotoxicity, an imbalance between lipogenesis de novo and fatty acid oxidation. Int J Obes Relat Metab Disord, 28 Suppl 4S22-8.
Li, Y., Xu, C., Yu, C., Xu, L., Miao, M. 2009. Association of serum uric acid level with non-alcoholic fatty liver disease: a cross-sectional study. Journal of hepatology, 50(5):1029-34.
Liu, L. F., Purushotham, A., Wendel, A. A., Koba, K., DeIuliis, J., Lee, K., Belury, M. A. 2009.
Regulation of adipose triglyceride lipase by rosiglitazone. Diabetes, obesity & metabolism, 11(2):131-42.
Loguercio, C., De Girolamo, V., de Sio, I., Tuccillo, C., Ascione, A., Baldi, F., Budillon, G., Cimino, L., Di Carlo, A., Di Marino, M. P. et al. 2001. Non-alcoholic fatty liver disease in an area of southern Italy: main clinical, histological, and pathophysiological aspects. Journal of hepatology, 35(5):568-74.
Loguercio, C., De Simone, T., D'Auria, M. V., de Sio, I., Federico, A., Tuccillo, C., Abbatecola, A. M., Del Vecchio Blanco, C. 2004. Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 36(6):398-405.
Ludwig, J., Viggiano, T. R., McGill, D. B., Oh, B. J. 1980. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic proceedings. Mayo Clinic, 55(7):434-8.
Man, M. Q., Barish, G. D., Schmuth, M., Crumrine, D., Barak, Y., Chang, S., Jiang, Y., Evans, R. M., Elias, P. M., Feingold, K. R. 2008. Deficiency of PPARbeta/delta in the epidermis results in defective cutaneous permeability barrier homeostasis and increased inflammation. The Journal of investigative dermatology, 128(2):370-7.
Mannaerts, G. P., Debeer, L. J., Thomas, J., De Schepper, P. J. 1979. Mitochondrial and peroxisomal fatty acid oxidation in liver homogenates and isolated hepatocytes from control and clofibrate-treated rats. The Journal of biological chemistry, 254(11):4585-95.
Martinez-Botas, J., Anderson, J. B., Tessier, D., Lapillonne, A., Chang, B. H., Quast, M. J., Gorenstein, D., Chen, K. H., Chan, L. 2000. Absence of perilipin results in leanness and reverses obesity in Lepr(db/db) mice. Nature genetics, 26(4):474-9.
Martinez-Clemente, M., Ferre, N., Gonzalez-Periz, A., Lopez-Parra, M., Horrillo, R., Titos, E., Moran-Salvador, E., Miquel, R., Arroyo, V., Funk, C. D. et al. 2010. 5-lipoxygenase deficiency reduces hepatic inflammation and tumor necrosis factor alpha-induced hepatocyte damage in hyperlipidemia-prone ApoE-null mice. Hepatology, 51(3):817-27.
Matteoni, C. A., Younossi, Z. M., Gramlich, T., Boparai, N., Liu, Y. C., McCullough, A. J. 1999.
Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology, 116(6):1413-9.
McGarry, J. D., Mannaerts, G. P., Foster, D. W. 1977. A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. J Clin Invest, 60(1):265-70.
Mello, T., Nakatsuka, A., Fears, S., Davis, W., Tsukamoto, H., Bosron, W. F., Sanghani, S. P. 2008.
Expression of carboxylesterase and lipase genes in rat liver cell-types. Biochemical and biophysical research communications, 374(3):460-464.
Miyoshi, H., Perfield, J. W., 2nd, Souza, S. C., Shen, W. J., Zhang, H. H., Stancheva, Z. S., Kraemer, F. B., Obin, M. S., Greenberg, A. S. 2007. Control of adipose triglyceride lipase action by serine 517 of perilipin A globally regulates protein kinase A-stimulated lipolysis in adipocytes. The Journal of biological chemistry, 282(2):996-1002.
Mizutani, Y., Mitsutake, S., Tsuji, K., Kihara, A., Igarashi, Y. 2009. Ceramide biosynthesis in keratinocyte and its role in skin function. Biochimie, 91(6):784-90.
Monetti, M., Levin, M. C., Watt, M. J., Sajan, M. P., Marmor, S., Hubbard, B. K., Stevens, R. D., Bain, J. R., Newgard, C. B., Farese, R. V., Sr. et al. 2007. Dissociation of hepatic steatosis and insulin resistance in mice overexpressing DGAT in the liver. Cell Metab, 6(1):69-78.
Neuschwander-Tetri, B. A., Bacon, B. R. 1996. Nonalcoholic steatohepatitis. The Medical clinics of North America, 80(5):1147-66.
Notari, L., Baladron, V., Aroca-Aguilar, J. D., Balko, N., Heredia, R., Meyer, C., Notario, P. M., Saravanamuthu, S., Nueda, M. L., Sanchez-Sanchez, F. et al. 2006. Identification of a lipase-linked cell membrane receptor for pigment epithelium-derived factor. The Journal of biological chemistry,281(49):38022-37.
Olivecrona, G. 2010. The crucial role of ATGL for energy supply of muscles. Journal of lipid research, 51(3):449-50.
Olsson, H., Stralfors, P., Belfrage, P. 1986. Phosphorylation of the basal site of hormone-sensitive lipase by glycogen synthase kinase-4. FEBS letters, 209(2):175-80.
Ong, K. T., Mashek, M. T., Bu, S. Y., Greenberg, A. S., Mashek, D. G. 2010. Adipose triglyceride lipase is a major hepatic lipase that regulates triacylglycerol turnover and fatty acid signaling and partitioning. Hepatology.
Osei-Hyiaman, D., Liu, J., Zhou, L., Godlewski, G., Harvey-White, J., Jeong, W. I., Batkai, S., Marsicano, G., Lutz, B., Buettner, C. et al. 2008. Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice. J Clin Invest, 118(9):3160-9.
Peyot, M. L., Guay, C., Latour, M. G., Lamontagne, J., Lussier, R., Pineda, M., Ruderman, N. B., Haemmerle, G., Zechner, R., Joly, E. et al. 2009. Adipose triglyceride lipase is implicated in fuel- and non-fuel-stimulated insulin secretion. The Journal of biological chemistry, 284(25):16848-59.
Ploeg, R. J., D'Alessandro, A. M., Knechtle, S. J., Stegall, M. D., Pirsch, J. D., Hoffmann, R. M., Sasaki, T., Sollinger, H. W., Belzer, F. O., Kalayoglu, M. 1993. Risk factors for primary dysfunction after liver transplantation--a multivariate analysis. Transplantation, 55(4):807-13.
Purushotham, A., Schug, T. T., Xu, Q., Surapureddi, S., Guo, X., Li, X. 2009. Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab, 9(4):327-38.
Radner, F. P., Streith, I. E., Schoiswohl, G., Schweiger, M., Kumari, M., Eichmann, T. O., Rechberger, G., Koefeler, H. C., Eder, S., Schauer, S. et al. 2010. Growth retardation, impaired triacylglycerol catabolism, hepatic steatosis, and lethal skin barrier defect in mice lacking comparative gene identification-58 (CGI-58). The Journal of biological chemistry, 285(10):7300-11.
Randle, P. J., Garland, P. B., Hales, C. N., Newsholme, E. A. 1963. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet, 1(7285):785-9.
Roduit, R., Masiello, P., Wang, S. P., Li, H., Mitchell, G. A., Prentki, M. 2001. A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice. Diabetes, 50(9):1970-5.
Rogalska, E., Cudrey, C., Ferrato, F., Verger, R. 1993. Stereoselective hydrolysis of triglycerides by animal and microbial lipases. Chirality, 5(1):24-30.
Russell, L., Forsdyke, D. R. 1991. A human putative lymphocyte G0/G1 switch gene containing a CpG-rich island encodes a small basic protein with the potential to be phosphorylated. DNA Cell Biol, 10(8):581-91.
Rydel, T. J., Williams, J. M., Krieger, E., Moshiri, F., Stallings, W. C., Brown, S. M., Pershing, J. C., Purcell, J. P., Alibhai, M. F. 2003. The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a Ser-Asp catalytic dyad. Biochemistry, 42(22):6696-708.
Schaffer, J. E. 2003. Lipotoxicity: when tissues overeat. Current opinion in lipidology, 14(3):281-7.
Schlosburg, J. E., Blankman, J. L., Long, J. Z., Nomura, D. K., Pan, B., Kinsey, S. G., Nguyen, P. T., Ramesh, D., Booker, L., Burston, J. J. et al. 2010. Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. Nat Neurosci, 13(9):1113-9.
Schoiswohl, G., Schweiger, M., Schreiber, R., Gorkiewicz, G., Preiss-Landl, K., Taschler, U., Zierler, K. A., Radner, F. P., Eichmann, T. O., Kienesberger, P. C. et al. 2010. Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids. Journal of lipid research, 51(3):490-9.
Schweiger, M., Lass, A., Zimmermann, R., Eichmann, T. O., Zechner, R. 2009. Neutral lipid storage disease: genetic disorders caused by mutations in adipose triglyceride lipase/PNPLA2 or CGI-58/ABHD5. American journal of physiology. Endocrinology and metabolism, 297(2):E289-96.
Schweiger, M., Schoiswohl, G., Lass, A., Radner, F. P., Haemmerle, G., Malli, R., Graier, W., Cornaciu, I., Oberer, M., Salvayre, R. et al. 2008. The C-terminal region of human adipose triglyceride lipase affects enzyme activity and lipid droplet binding. The Journal of biological chemistry, 283(25):17211-20.
Schweiger, M., Schreiber, R., Haemmerle, G., Lass, A., Fledelius, C., Jacobsen, P., Tornqvist, H., Zechner, R., Zimmermann, R. 2006. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism. The Journal of biological chemistry, 281(52):40236-41.
Schwimmer, J. B., Behling, C., Newbury, R., Deutsch, R., Nievergelt, C., Schork, N. J., Lavine, J. E. 2005. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology, 42(3):641-9.
Sheriff, S., Du, H., Grabowski, G. A. 1995. Characterization of lysosomal acid lipase by site-directed mutagenesis and heterologous expression. J Biol Chem, 270(46):27766-72.
Shewry, P. R. 2003. Tuber storage proteins. Ann Bot, 91(7):755-69.
Silverman, J. F., O'Brien, K. F., Long, S., Leggett, N., Khazanie, P. G., Pories, W. J., Norris, H. T., Caro, J. F. 1990. Liver pathology in morbidly obese patients with and without diabetes. The American journal of gastroenterology, 85(10):1349-55.
Singh, R., Kaushik, S., Wang, Y., Xiang, Y., Novak, I., Komatsu, M., Tanaka, K., Cuervo, A. M., Czaja, M. J. 2009a. Autophagy regulates lipid metabolism. Nature, 458(7242):1131-5.
Singh, R., Wang, Y., Xiang, Y., Tanaka, K. E., Gaarde, W. A., Czaja, M. J. 2009b. Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology, 49(1):87-96.
Sirois, J., Cote, J. F., Charest, A., Uetani, N., Bourdeau, A., Duncan, S. A., Daniels, E., Tremblay, M. L. 2006. Essential function of PTP-PEST during mouse embryonic vascularization, mesenchyme formation, neurogenesis and early liver development. Mech Dev, 123(12):869-80.
Slawik, M., Vidal-Puig, A. J. 2006. Lipotoxicity, overnutrition and energy metabolism in aging. Ageing Res Rev, 5(2):144-64.
Soni, K. G., Mardones, G. A., Sougrat, R., Smirnova, E., Jackson, C. L., Bonifacino, J. S. 2009a.
Coatomer-dependent protein delivery to lipid droplets. Journal of cell science, 122(Pt 11):1834-41.
Soni, K. G., Mardones, G. A., Sougrat, R., Smirnova, E., Jackson, C. L., Bonifacino, J. S. 2009b.
Coatomer-dependent protein delivery to lipid droplets. Journal of cell science, 122(Pt 11):1834-41.
Stumptner, C., Fuchsbichler, A., Heid, H., Zatloukal, K., Denk, H. 2002. Mallory body--a disease-associated type of sequestosome. Hepatology, 35(5):1053-62.
Subramanian, V., Rothenberg, A., Gomez, C., Cohen, A. W., Garcia, A., Bhattacharyya, S., Shapiro, L., Dolios, G., Wang, R., Lisanti, M. P. et al. 2004. Perilipin A mediates the reversible binding of CGI-58 to lipid droplets in 3T3-L1 adipocytes. The Journal of biological chemistry, 279(40):42062-71.
Sztalryd, C., Xu, G., Dorward, H., Tansey, J. T., Contreras, J. A., Kimmel, A. R., Londos, C. 2003.
Perilipin A is essential for the translocation of hormone-sensitive lipase during lipolytic activation. The Journal of cell biology, 161(6):1093-103.
Tang, J., Kriz, R. W., Wolfman, N., Shaffer, M., Seehra, J., Jones, S. S. 1997. A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs. The Journal of biological chemistry, 272(13):8567-75.
Tansey, J. T., Huml, A. M., Vogt, R., Davis, K. E., Jones, J. M., Fraser, K. A., Brasaemle, D. L., Kimmel, A. R., Londos, C. 2003. Functional studies on native and mutated forms of perilipins. A role in protein kinase A-mediated lipolysis of triacylglycerols. The Journal of biological chemistry, 278(10):8401-6.
Taschler, U., Radner, F. P., Heier, C., Schreiber, R., Schweiger, M., Schoiswohl, G., Preiss-Landl, K., Jaeger, D., Reiter, B., Koefeler, H. C. et al. 2011. Monoglyceride lipase-deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. The Journal of biological chemistry.
Tiniakos, D. G., Vos, M. B., Brunt, E. M. 2010. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annual review of pathology, 5145-71.
van Kempen, A. A., van der Crabben, S. N., Ackermans, M. T., Endert, E., Kok, J. H., Sauerwein, H. P. 2006. Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile. Am J Physiol Endocrinol Metab, 290(4):E723-30.
Villena, J. A., Roy, S., Sarkadi-Nagy, E., Kim, K. H., Sul, H. S. 2004. Desnutrin, an adipocyte gene encoding a novel patatin domain-containing protein, is induced by fasting and glucocorticoids: ectopic expression of desnutrin increases triglyceride hydrolysis. The Journal of biological chemistry, 279(45):47066-75.
Wang, H., Hu, L., Dalen, K., Dorward, H., Marcinkiewicz, A., Russell, D., Gong, D., Londos, C., Yamaguchi, T., Holm, C. et al. 2009. Activation of hormone-sensitive lipase requires two steps, protein phosphorylation and binding to the PAT-1 domain of lipid droplet coat proteins. The Journal of biological chemistry, 284(46):32116-25.
Wang, S. P., Laurin, N., Himms-Hagen, J., Rudnicki, M. A., Levy, E., Robert, M. F., Pan, L., Oligny, L., Mitchell, G. A. 2001. The adipose tissue phenotype of hormone-sensitive lipase deficiency in mice. Obes Res, 9(2):119-28.
Wang, S. P., Marth, J. D., Oligny, L. L., Vachon, M., Robert, M. F., Ashmarina, L., Mitchell, G. A. 1998. 3-Hydroxy-3-methylglutaryl-CoA lyase (HL): gene targeting causes prenatal lethality inHL-deficient mice. Hum Mol Genet, 7(13):2057-62.
Watt, M. J., Spriet, L. L. 2004. Regulation and role of hormone-sensitive lipase activity in human skeletal muscle. The Proceedings of the Nutrition Society, 63(2):315-22.
Wei, E., Ben Ali, Y., Lyon, J., Wang, H., Nelson, R., Dolinsky, V. W., Dyck, J. R., Mitchell, G., Korbutt, G. S., Lehner, R. 2010. Loss of TGH/Ces3 in mice decreases blood lipids, improves glucose tolerance, and increases energy expenditure. Cell Metab, 11(3):183-93.
Wu, Q., Ortegon, A. M., Tsang, B., Doege, H., Feingold, K. R., Stahl, A. 2006. FATP1 is an insulin-sensitive fatty acid transporter involved in diet-induced obesity. Mol Cell Biol, 26(9):3455-67.
Yang, Q., Graham, T. E., Mody, N., Preitner, F., Peroni, O. D., Zabolotny, J. M., Kotani, K., Quadro, L., Kahn, B. B. 2005. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature, 436(7049):356-62.
Yang, X., Lu, X., Lombes, M., Rha, G. B., Chi, Y. I., Guerin, T. M., Smart, E. J., Liu, J. 2010. The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase. Cell Metab, 11(3):194-205.
Yeaman, S. J. 2004. Hormone-sensitive lipase--new roles for an old enzyme. The Biochemical journal, 379(Pt 1):11-22.
Zafrani, E. S. 2004. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Archiv : an international journal of pathology, 444(1):3-12.
Zimmermann, R., Strauss, J. G., Haemmerle, G., Schoiswohl, G., Birner-Gruenberger, R., Riederer, M., Lass, A., Neuberger, G., Eisenhaber, F., Hermetter, A. et al. 2004. Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science, 306(5700):1383-6.