Revisiting the connection between intramyocellular lipids and insulin resistance: a long and winding road

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• 作者：D. M. Muoio (123) muoio@duke.edu
• 关键词：Diabetes – ; Fatty acids – ; Insulin resistance – ; Intramyocellular triacylglycerol – ; Lipid droplet – ; Muscle – ; NMR – ; Obesity
• 刊名：Diabetologia
• 出版年：2012
• 出版时间：October 2012
• 年：2012
• 卷：55
• 期：10
• 页码：2551-2554
• 全文大小：179.1 KB
• 参考文献：1. Lithell H, Orlander J, Schele R, Sjodin B, Karlsson J (1979) Changes in lipoprotein-lipase activity and lipid stores in human skeletal muscle with prolonged heavy exercise. Acta Physiol Scand 107:257–261
  2. Hurley BF, Nemeth PM 3rd, Martin WH, Hagberg JM, Dalsky GP, Holloszy JO (1986) Muscle triglyceride utilization during exercise: effect of training. J Appl Physiol 60:562–567
  3. Muoio DM (2010) Intramuscular triacylglycerol and insulin resistance: guilty as charged or wrongly accused? Biochim Biophys Acta 1801:281–288
  4. Muoio DM, Newgard CB (2008) Mechanisms of disease: molecular and metabolic mechanisms of insulin resistance and beta-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9:193–205
  5. McGarry JD (2002) Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51:7–18
  6. Randle PJ (1998) Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 14:263–283 (Review)
  7. Krssak M, Falk Petersen K, Dresner A et al (1999) Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 42:113–116
  8. Unger RH (2003) Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 144:5159–5165
  9. Goodpaster BH, He J, Watkins S, Kelley DE (2001) Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes. J Clin Endocrinol Metab 86:5755–5761
  10. Schenk S, Horowitz JF (2007) Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance. J Clin Invest 117:1690–1698
  11. Liu L, Zhang Y, Chen N, Shi X, Tsang B, Yu YH (2007) Upregulation of myocellular DGAT1 augments triglyceride synthesis in skeletal muscle and protects against fat-induced insulin resistance. J Clin Invest 117:1679–1689
  12. Fujimoto T, Parton RG (2011) Not just fat: the structure and function of the lipid droplet. Cold Spring Harb Perspect Biol 3:pii:a004838
  13. Haemmerle G, Moustafa T, Woelkart G et al (2011) ATGL-mediated fat catabolism regulates cardiac mitochondrial function via PPAR-α and PGC-1. Nat Med 17:1076–1085
• 作者单位：1. Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA2. Department of Medicine, Duke University, Durham, NC, USA3. Department of Pharmacology & Cancer Biology, Duke University, Durham, NC, USA
• ISSN：1432-0428

文摘

In the mid-1990s, researchers began to re-examine type 2 diabetes from a more ‘lipocentric’ perspective; giving strong consideration to the idea that systemic lipid imbalances give rise to glucose dysregulation, rather than vice versa. At the forefront of this paradigm shift was a report by Krssak and colleagues (Diabetologia 1999; 42:113–116) showing that intramyocellular lipid content, measured via the (then) novel application of proton nuclear magnetic resonance spectroscopy, served as a robust indicator of muscle insulin sensitivity in healthy individuals. A subsequent wave of investigations produced compelling correlative evidence linking ectopic lipid deposition within skeletal myocytes to the development of obesity-associated insulin resistance. But this relationship has proven much more complex than originally imagined, and scientists today are still left wondering if and how the intramyocellular accumulation of lipid droplets has a direct bearing on insulin action. Originally viewed as a simple storage depot, the lipid droplet is now recognised as an essential and sophisticated organelle that actively participates in numerous cellular processes. This edition of ‘Then and now’ revisits the connection between intramuscular lipids and insulin resistance and looks to future research aimed at understanding the dynamic interplay between lipid droplet biology and metabolic health.