1. Re-evaluating lipotoxic triggers in skeletal muscle: Relating intramyocellular lipid metabolism to insulin sensitivity
- Author
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Sander Kersten, Patrick Schrauwen, Madeleen Bosma, Matthijs K. C. Hesselink, Humane Biologie, Nutrition and Movement Sciences, and RS: NUTRIM - R1 - Metabolic Syndrome
- Subjects
Muscle Proteins ,kinase-c activation ,Type 2 diabetes ,adipose-tissue ,Biochemistry ,Ceramide ,Voeding, Metabolisme en Genomica ,chemistry.chemical_compound ,Lipid droplet ,Insulin ,saturated fatty-acids ,KINASE-C ACTIVATION ,morbidly obese subjects ,SATURATED FATTY-ACIDS ,STEAROYL-COA DESATURASE ,LEPTIN-DEFICIENT MICE ,stearoyl-coa desaturase ,Metabolism and Genomics ,ADIPOSE-TISSUE ,medicine.anatomical_structure ,Lipotoxicity ,Metabolisme en Genomica ,Nutrition, Metabolism and Genomics ,lipids (amino acids, peptides, and proteins) ,leptin-deficient mice ,Diacylglycerol ,weight-loss ,Athlete's paradox ,medicine.medical_specialty ,TYPE-2 DIABETIC-PATIENTS ,WEIGHT-LOSS ,Biology ,Insulin resistance ,Voeding ,MORBIDLY OBESE SUBJECTS ,Internal medicine ,MAGNETIC-RESONANCE SPECTROSCOPY ,medicine ,Animals ,Humans ,magnetic-resonance spectroscopy ,Muscle, Skeletal ,VLAG ,Nutrition ,Diacylglycerol kinase ,Skeletal muscle ,Lipid metabolism ,Cell Biology ,Lipid Metabolism ,Lipid droplets ,medicine.disease ,Endocrinology ,chemistry ,DIFFERENTIATION-RELATED PROTEIN ,differentiation-related protein ,type-2 diabetic-patients - 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.
- Published
- 2012
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