Effects of high-fat diet and caloric restriction on skeletal muscle gene expression in rhesus macaques

Reduced physical activity and increased caloric intake are the main risk factors for obesity. The present study addressed the transcriptional dynamics in skeletal muscle of rhesus macaque after animals were exposed to a high-fat Western-style diet (WSD) and then after caloric restriction without exercise. Soleus muscle biopsies were subjected to longitudinal gene expression analysis using RNA-Seq. In spite of significant weight loss and improved insulin sensitivity, calorically restricted animals continued to display gene expression signatures that were induced by WSD. While energy metabolism genes remained downregulated, TGFb pathways genes remained upregulated after caloric restriction. Thus, caloric restriction can reduce obesity and insulin resistance, but a subset of WSD-specific genes remained dysregulated after the reversal of obesity, suggesting that SM transcriptome can develop the lasting memory in response to overnutrition.