Long-lasting effect of obesity on skeletal muscle transcriptome

BMC Genomics

Judy L. Cameron¹  Ruhee Jain¹  Byung S. Park²  Kerri M. Winters-Stone³  Maham Rais⁴  Oleg Varlamov⁵  Mithila Handu⁵  Ashley E. White⁵  Suzanne S. Fei⁶  Hollis Wright⁶  Ilhem Messaoudi⁷  Suhas Sureshchandra⁷ 

[1] Department of Neuroscience and Psychiatry, University of Pittsburgh;Department of Public Health and Preventive Medicine, Oregon Health and Science University;Department of School of Nursing, Oregon Health and Science University;Division of Biomedical Sciences, School of Medicine, University of California, Riverside;Division of Cardiometabolic Health, Oregon National Primate Research Center;Division of Neuroscience, Oregon National Primate Research Center;School of Biological Sciences, University of California, Irvine;

关键词: Insulin resistance;    Caloric restriction;    High-fat diet;    Skeletal muscle;    Obesity;   

DOI  :  10.1186/s12864-017-3799-y

来源: DOAJ

【 摘 要 】

Abstract Background Reduced physical activity and increased intake of calorically-dense diets are the main risk factors for obesity, glucose intolerance, and type 2 diabetes. Chronic overnutrition and hyperglycemia can alter gene expression, contributing to long-term obesity complications. While caloric restriction can reduce obesity and glucose intolerance, it is currently unknown whether it can effectively reprogram transcriptome to a pre-obesity level. The present study addressed this question by the preliminary examination of the transcriptional dynamics in skeletal muscle after exposure to overnutrition and following caloric restriction. Results Six male rhesus macaques of 12–13 years of age consumed a high-fat western-style diet for 6 months and then were calorically restricted for 4 months without exercise. Skeletal muscle biopsies were subjected to longitudinal gene expression analysis using next-generation whole-genome RNA sequencing. In spite of significant weight loss and normalized insulin sensitivity, the majority of WSD-induced (n = 457) and WSD-suppressed (n = 47) genes remained significantly dysregulated after caloric restriction (FDR ≤0.05). The MetacoreTM pathway analysis reveals that western-style diet induced the sustained activation of the transforming growth factor-β gene network, associated with extracellular matrix remodeling, and the downregulation of genes involved in muscle structure development and nutritional processes. Conclusions Western-style diet, in the absence of exercise, induced skeletal muscle transcriptional programing, which persisted even after insulin resistance and glucose intolerance were completely reversed with caloric restriction.

【 授权许可】

Unknown