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Re-evaluating lipotoxic triggers in skeletal muscle: relating intramyocellular lipid metabolism to insulin sensitivity |
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| Authors: | Bosma Madeleen Kersten Sander Hesselink Matthijs K C Schrauwen Patrick |
| Affiliation: | a Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, 6200MD Maastricht, The Netherlands b Nutrition, Metabolism and Genomics Group, Division of Human Nutrition, Wageningen University, 6700EV Wageningen, The Netherlands c Human Movement Sciences, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center+, 6200MD Maastricht, The Netherlands |
| Abstract: | Ectopic fat accumulation has been linked to lipotoxic events, including the development of insulin resistance in skeletal muscle. Indeed, intramyocellular lipid storage is strongly associated with the development of type 2 diabetes. Research during the last two decades has provided evidence for a role of lipid intermediates like diacylglycerol and ceramide in the induction of lipid-induced insulin resistance. However, recently novel data has been gathered that suggest that the relation between lipid intermediates and insulin resistance is less straightforward than has been previously suggested, and that there are several routes towards lipid-induced insulin resistance. For example, research in this field has shifted towards imbalances in lipid metabolism and lipid droplet dynamics. Next to imbalances in key lipogenic and lipolytic proteins, lipid droplet coat proteins appear to be essential for proper intramyocellular lipid storage, turnover and protection against lipid-induced insulin resistance.Here, we discuss the current knowledge on lipid-induced insulin resistance in skeletal muscle with a focus on the evidence from human studies. Furthermore, we discuss the available data that provides supporting mechanistic information. |
| Keywords: | ACS, acyl-CoA transferase AcylCarn, acylcarnitines ATGL, adipose triglyceride lipase CPT1, carnitine palmitoyltransferase-1 DAG, diacylglycerol DGAT, diacylglycerol acyltransferase DGK, diacylglycerol kinase EM, electron microscopy FA, fatty acid FFA, free fatty acid GPAT, glycerol 3-phosphate acyltransferase HSL, hormone-sensitive lipase IMCL, intramyocellular lipids IMTG, intramyocellular triacylglycerol IRS-1, insulin receptor substrate 1 IS, insulin sensitivity LCFA-CoA, long chain fatty acyl-CoA LD, lipid droplet MAG, monoacylglycerol MGAT, monoacylglycerol acyltransferase MGL, monoglyceride lipase NGT, normal glucose tolerant PA, phosphatidic acid PFK1, phosphofructokinase-1 PKC, protein kinase C PLIN, perilipin PP2A, protein phosphatase 2A SCD1, stearol-CoA desaturase-1 T2DM, type 2 diabetes mellitus TAG, triacylglycerol TCA, tricarboxylic acid cycle |
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