非酯化脂肪酸与代谢性炎症相关性的研究进展
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摘要
代谢性炎症是由多种细胞与细胞因子介导的慢性低度炎症反应,与代谢性疾病的致病机制紧密相关,已成为目前的研究热点。NEFA作为机体重要的代谢产物和能源物质,在多种代谢性疾病如肥胖、Ⅱ型糖尿病等疾病中起着关键作用。本文就NEFA与代谢性炎症相关联的几种慢性炎症机制进行简单综述。
Metabolic inflammation referred to chronic low-grade inflammation is transmitted by multiple cells and cytokines,and has a close association with metabolic disease. It has been one of the focused research topics. NEFA as an important metabolite and source of energy,plays a key role in multiple metabolic diseases such as obesity and type 2 diabetes. This review focuses on the mechanistic link between the NEFA and metabolic inflammation.
Metabolic inflammation referred to chronic low-grade inflammation is transmitted by multiple cells and cytokines,and has a close association with metabolic disease. It has been one of the focused research topics. NEFA as an important metabolite and source of energy,plays a key role in multiple metabolic diseases such as obesity and type 2 diabetes. This review focuses on the mechanistic link between the NEFA and metabolic inflammation.
引文
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[13] Ringseis R,Eder K,Mooren FC,et al. Metabolic signals and innate immune activation in obesity and exercise[J]. Exerc Immunol Rev,2015,21:58.
[14] Konner AC,Bruning JC. Selective insulin and leptin resistance in metabolic disorders[J]. Cell Metab,2012,16(2):144-152.
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[16] Borst SE. The role of TNF-αin insulin resistance[J]. Endocrine,2004,23(2-3):177-182.
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[18] Shi X,Li D,Deng Q,et al. NEFAs activate the oxidative stressmediated NF-kappaB signaling pathway to induce inflammatory response in calf hepatocytes[J]. J Steroid Biochem,2015,145:103-112.
[19] Krautbauer S,Eisinger K,Neumeier M,et al. Free fatty acids,lipopolysaccharide and IL-1alpha induce adipocyte manganese superoxide dismutase which is increased in visceral adipose tissues of obese rodents[J]. PLo S One,2014,9(1):e86866.
[20] Kanda H,Tateya S,Tamori Y,et al. MCP-1 contributes to macrophage infiltration into adipose tissue,insulin resistance,and hepatic steatosis in obesity[J]. J Clin Invest,2006,116(6):1494-1505.
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[22] Wong SW,Kwon MJ,Choi AM,et al. Fatty acids modulate Tolllike receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner[J]. J Biol Chem,2009,284(40):27384-27392.
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[24] Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease[J]. Cell,2010,140(6):900-917.
[25] Bunn RC,Cockrell GE,Ou Y,et al. Palmitate and insulin synergistically induce IL-6 expression in human monocytes[J].Cardiovasc Diabetol,2010,9:73.
[26] Wang C,Li Y,Hao M,et al. AstragalosideⅣinhibits triglyceride accumulation in insulin-resistant HepG2 cells via AMPK-Induced SREBP-1c phosphorylation[J]. Front Pharmacol,2018,9:345.
[27] Kumashiro N,Erion DM,Zhang D,et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease[J]. Proc Natl Acad Sci USA,2011,108(39):16381-16385.
[28] Lin Y,Berg AH,Iyengar P,et al. The hyperglycemia-induced inflammatory response in adipocytes:the role of reactive oxygen species[J]. J Biol Chem,2005,280(6):4617-4626.
[29] Stewart CR,Stuart LM,Wilkinson K,et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and6 heterodimer[J]. Nat Immunol,2010,11(2):155-161.
[30] Zhong S,Zhao L,Wang Y,et al. Cluster of differentiation 36deficiency aggravates macrophage infiltration and hepatic inflammation by upregulating monocyte chemotactic protein-1expression of hepatocytes through histone deacetylase 2-dependent pathway[J]. Antioxid Redox Sign,2017,27(4):201-214.
[31] Miquilena-Colina ME,Lima-Cabello E,Sanchez-Campos S,et al.Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance,hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C[J]. Gut,2011,60(10):1394-1402.
[32] Hollestelle SC,De Vries MR,Van Keulen JK,et al. Toll-like receptor 4 is involved in outward arterial remodeling[J].Circulation,2004,109(3):393-398.
[33] Dasu MR,Jialal I. Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors[J]. Am J Physiol-Endoc M,2015,300(1):145-154.
[34] Hussey SE,Lum H,Alvarez A,et al. A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle[J]. Diabetologia,2014,57(3):582-591.
[35] Yuan M,Konstantopoulos N,Lee J,et al. Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ[J]. Science,2001,293(5535):1673.
[36] Minegishi Y,Haramizu S,Misawa K,et al. Deletion of nuclear factor-κB p50 upregulates fatty acid utilization and contributes to an anti-obesity and high-endurance phenotype in mice[J]. Am J Physiol-Endoc M,2015,309(6):E523.
[37] Li X,Huang W,Gu J,et al. SREBP-1c overactivates ROSmediated hepatic NF-kappaB inflammatory pathway in dairy cows with fatty liver[J]. Cell Signal,2015,27(10):2099-2109.
[2] Bradford BJ,Yuan K,Farney JK,et al. Invited review:Inflammation during the transition to lactation:New adventures with an old flame[J]. J Dairy Sci,2015,98(10):6631-6650.
[3] Gregor MF,Hotamisligil GS. Inflammatory mechanisms in obesity[J]. Annu Rev Immunol,2011,29:415-445.
[4] Esser N,Legrand-Poels S,Piette J,et al. Inflammation as a link between obesity,metabolic syndrome and type 2 diabetes[J].Diabetes Res Clin Pr,2014,105(2):141-150.
[5] Sommerfeld A,Reinehr R,Hussinger D. Free fatty acids shift insulin-induced hepatocyte proliferation towards CD95-dependent apoptosis[J]. J Biol Chem,2015,290(7):4398-4409.
[6] Frommer KW,Schaffler A,Rehart S,et al. Free fatty acids:potential proinflammatory mediators in rheumatic diseases[J]. Ann Rheum Dis,2015,74(1):303-310.
[7] Legrand-Poels S,Esser N,L'Homme L,et al. Free fatty acids as modulators of the NLRP3 inflammasome in obesity/type 2 diabetes[J]. Bioche Pharmacol,2014,92(1):131-141.
[8] Oh YT,Kim J,Kang I,et al. Regulation of hypothalamic-pituitaryadrenal axis by circulating free fatty acids in male Wistar rats:role of individual free fatty acids[J]. Endocrinology,2014,155(3):923-931.
[9] Boden G. Obesity,insulin resistance and free fatty acids[J]. Curr Opin Endocrinol Diabetes Obes,2011,18(2):139-143.
[10] Gruzdeva O,Uchasova E,Dyleva Y,et al. Multivessel coronary artery disease,free fatty acids,oxidized LDL and its antibody in myocardial infarction[J]. Lipids Health Dis,2014,13(1):111.
[11] Portillo Sanchez P,Bril F,Maximos M,et al. High prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus and normal plasma aminotransferase levels[J]. J Clin Endocr Metab,2014,100(5):doi:10. 1210/jc. 2014-2739.
[12] Kwok KH,Cheng KK,Hoo RL,et al. Adipose-specific inactivation of JNK alleviates atherosclerosis in apoE-deficient mice[J]. Clin Sci,2016,130(22):2087-2100.
[13] Ringseis R,Eder K,Mooren FC,et al. Metabolic signals and innate immune activation in obesity and exercise[J]. Exerc Immunol Rev,2015,21:58.
[14] Konner AC,Bruning JC. Selective insulin and leptin resistance in metabolic disorders[J]. Cell Metab,2012,16(2):144-152.
[15] Hotamisligil GS,Shargill NS,Spiegelman BM. Adipose expression of tumor necrosis factor-alpha:direct role in obesity-linked insulin resistance[J]. Science,1993,259(5091):87.
[16] Borst SE. The role of TNF-αin insulin resistance[J]. Endocrine,2004,23(2-3):177-182.
[17] Lfgren P,Van HV,Reynisdottir S,et al. Secretion of tumor necrosis factor-alpha shows a strong relationship to insulinstimulated glucose transport in human adipose tissue[J].Diabetes,2000,49(5):688-692.
[18] Shi X,Li D,Deng Q,et al. NEFAs activate the oxidative stressmediated NF-kappaB signaling pathway to induce inflammatory response in calf hepatocytes[J]. J Steroid Biochem,2015,145:103-112.
[19] Krautbauer S,Eisinger K,Neumeier M,et al. Free fatty acids,lipopolysaccharide and IL-1alpha induce adipocyte manganese superoxide dismutase which is increased in visceral adipose tissues of obese rodents[J]. PLo S One,2014,9(1):e86866.
[20] Kanda H,Tateya S,Tamori Y,et al. MCP-1 contributes to macrophage infiltration into adipose tissue,insulin resistance,and hepatic steatosis in obesity[J]. J Clin Invest,2006,116(6):1494-1505.
[21] Maury E,Brichard SM. Adipokine dysregulation,adipose tissue inflammation and metabolic syndrome[J]. Mol Cell Endocrinol,2010,314(1):1-16.
[22] Wong SW,Kwon MJ,Choi AM,et al. Fatty acids modulate Tolllike receptor 4 activation through regulation of receptor dimerization and recruitment into lipid rafts in a reactive oxygen species-dependent manner[J]. J Biol Chem,2009,284(40):27384-27392.
[23] Shi H,Kokoeva MV,Inouye K,et al. TLR4 links innate immunity and fatty acid-induced insulin resistance[J]. J Clin Invest,2006,116(11):3015-3025.
[24] Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease[J]. Cell,2010,140(6):900-917.
[25] Bunn RC,Cockrell GE,Ou Y,et al. Palmitate and insulin synergistically induce IL-6 expression in human monocytes[J].Cardiovasc Diabetol,2010,9:73.
[26] Wang C,Li Y,Hao M,et al. AstragalosideⅣinhibits triglyceride accumulation in insulin-resistant HepG2 cells via AMPK-Induced SREBP-1c phosphorylation[J]. Front Pharmacol,2018,9:345.
[27] Kumashiro N,Erion DM,Zhang D,et al. Cellular mechanism of insulin resistance in nonalcoholic fatty liver disease[J]. Proc Natl Acad Sci USA,2011,108(39):16381-16385.
[28] Lin Y,Berg AH,Iyengar P,et al. The hyperglycemia-induced inflammatory response in adipocytes:the role of reactive oxygen species[J]. J Biol Chem,2005,280(6):4617-4626.
[29] Stewart CR,Stuart LM,Wilkinson K,et al. CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and6 heterodimer[J]. Nat Immunol,2010,11(2):155-161.
[30] Zhong S,Zhao L,Wang Y,et al. Cluster of differentiation 36deficiency aggravates macrophage infiltration and hepatic inflammation by upregulating monocyte chemotactic protein-1expression of hepatocytes through histone deacetylase 2-dependent pathway[J]. Antioxid Redox Sign,2017,27(4):201-214.
[31] Miquilena-Colina ME,Lima-Cabello E,Sanchez-Campos S,et al.Hepatic fatty acid translocase CD36 upregulation is associated with insulin resistance,hyperinsulinaemia and increased steatosis in non-alcoholic steatohepatitis and chronic hepatitis C[J]. Gut,2011,60(10):1394-1402.
[32] Hollestelle SC,De Vries MR,Van Keulen JK,et al. Toll-like receptor 4 is involved in outward arterial remodeling[J].Circulation,2004,109(3):393-398.
[33] Dasu MR,Jialal I. Free fatty acids in the presence of high glucose amplify monocyte inflammation via Toll-like receptors[J]. Am J Physiol-Endoc M,2015,300(1):145-154.
[34] Hussey SE,Lum H,Alvarez A,et al. A sustained increase in plasma NEFA upregulates the Toll-like receptor network in human muscle[J]. Diabetologia,2014,57(3):582-591.
[35] Yuan M,Konstantopoulos N,Lee J,et al. Reversal of obesity-and diet-induced insulin resistance with salicylates or targeted disruption of Ikkβ[J]. Science,2001,293(5535):1673.
[36] Minegishi Y,Haramizu S,Misawa K,et al. Deletion of nuclear factor-κB p50 upregulates fatty acid utilization and contributes to an anti-obesity and high-endurance phenotype in mice[J]. Am J Physiol-Endoc M,2015,309(6):E523.
[37] Li X,Huang W,Gu J,et al. SREBP-1c overactivates ROSmediated hepatic NF-kappaB inflammatory pathway in dairy cows with fatty liver[J]. Cell Signal,2015,27(10):2099-2109.