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

OBJECTIVE Diet intervention in obese adults is the first strategy to induce weight loss and to 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. RESEARCH DESIGN AND METHODS Eight obese, insulin resistant, non-diabetic adults were recruited to participate in a three-week low calorie diet intervention study (1000 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. RESULTS Body weight was reduced, insulin sensitivity (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 oxidative phosphorylation and inflammatory processes were among the most enriched KEGG-pathways identified after dietary intervention. mRNA expression of PDK4 and MLYCD increased, while SCD 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. CONCLUSIONS 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. Overall design: Eight obese non-diabetic (two men and six women) participants were recruited to enroll in the study. Two of the participants were on hypertensive medication (calcium channel blocker, Amlodipin and ACE inhibitor, Enalapril), and one participant was on medication for hyperlipidemia (HMG-CoA reductase inhibitor, Simvastatin). Participants with a fasting plasma glucose of >7 mmol/L or with medication for type 2 diabetes were not enrolled in the study. The participants underwent a three-week (23±9 days) low calorie diet consisting of 1000 kcal/day (40-50% carbohydrate, 30-40% protein and 20% fat as percentage of the total calories). All meals were replaced with nutritional formulas from various manufacturers (Modifast, Allévo or Nutrilett) and the participants could select the products to achieve the daily 1000 kcal. Informed written consent was obtained from the participants. The study was approved by the regional ethics committee of Stockholm and conducted according to the Declaration of Helsinki.