Short-term low-calorie diet remodels skeletal muscle lipid profile and metabolic gene expression in obese adults.

Diet intervention in obese adults is the first strategy to induce weight loss and improve insulin sensitivity. We hypothesized that improvements in insulin sensitivity after weight loss from a short-term dietary intervention tracks with alterations in expression of metabolic genes and abundance of specific lipid species. Eight obese, insulin-resistant, nondiabetic adults were recruited to participate in a 3-wk low-calorie diet intervention cohort study (1,000 kcal/day). Fasting blood samples and vastus lateralis skeletal muscle biopsies were obtained before and after the dietary intervention. Clinical chemistry and measures of insulin sensitivity were determined. Unbiased microarray gene expression and targeted lipidomic analysis of skeletal muscle was performed. Body weight was reduced, insulin sensitivity [measured by homeostatic model assessment of insulin resistance, (HOMA-IR)] was enhanced, and serum insulin concentration and blood lipid (triglyceride, cholesterol, LDL, and HDL) levels were improved after dietary intervention. Gene set enrichment analysis of skeletal muscle revealed that biosynthesis of unsaturated fatty acid was among the most enriched pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD1 decreased in skeletal muscle after dietary intervention. Dietary intervention altered the intramuscular lipid profile of skeletal muscle, with changes in content of phosphatidylcholine and triglyceride species among the pronounced. Short-term diet intervention and weight loss in obese adults alters metabolic gene expression and reduces specific phosphatidylcholine and triglyceride species in skeletal muscle, concomitant with improvements in clinical outcomes and enhanced insulin sensitivity.