Effect of Weight Loss on Skeletal Muscle Bioactive Lipids in People With Obesity and Type 2 Diabetes.

Muscle sn -1,2-diacylglycerol (DAG) and C18:0 ceramide accumulation in sarcolemmal and mitochondrial compartments have been proposed to regulate muscle insulin sensitivity. Here, we evaluated whether weight loss-induced improvements in insulin sensitivity were associated with changes in muscle sn -1,2-DAG and ceramide content in people with obesity and type 2 diabetes. We measured skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose tracer infusion, and skeletal muscle sn -1,2-DAG and ceramide contents by using liquid chromatography–tandem mass spectrometry after subcellular fractionation and DAG isomer separation in 14 adults with obesity and type 2 diabetes before and after marked (18.6 ± 2.1%) weight loss. Whole-body insulin sensitivity doubled after weight loss. Sarcolemmal sn -1,2-DAG and C18:0 ceramide contents after weight loss were not different from values before weight loss. In contrast, mitochondrial-endoplasmic reticulum (ER) C18:0 ceramide content decreased by ∼20% after weight loss (from 2.16 ± 0.08 to 1.71 ± 0.13 nmol/g, P < 0.005). These results suggest a decrease in muscle mitochondrial-ER C18:0 ceramide content could contribute to the beneficial effect of weight loss on skeletal muscle insulin sensitivity. Article Highlights: Importance of changes in muscle sn -1,2-diacylglycerols (DAG) or C18:0 ceramide in mediating the beneficial effects of weight loss on muscle insulin sensitivity in people is not known. We examined whether weight loss–induced increases in muscle insulin sensitivity in people with obesity and type 2 diabetes are accompanied by changes in muscle sn -1,2-DAG or C18:0 ceramide. Weight loss improved muscle insulin sensitivity, which was accompanied by a 20% decrease in mitochondrial–endoplasmic reticulum C18:0 ceramide without a change in sarcolemmal C18:0 ceramide or sn -1,2-DAG. These results suggest that decreased muscle mitochondrial–endoplasmic reticulum C18:0 ceramide content contributes to the beneficial effect of weight loss on muscle insulin sensitivity. [ABSTRACT FROM AUTHOR]

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