Comprehensive interrogation of human skeletal muscle reveals a dissociation between insulin resistance and mitochondrial capacity
Katie L. Whytock, Maria F. Pino, Yifei Sun, Gongxin Yu, Flávia Giolo de Carvalho, Reichelle X. Yeo, Rick B. Vega, Gaganvir Parmar, Adeline Divoux, Nidhi Kapoor, Fancaho Yi, Heather Cornnell, David A. Patten, Mary‐Ellen Harper, Stephen J. Gardell, Steven R. Smith, Martin J. Walsh, Lauren M. Sparks
Abstract
Whether impaired mitochondrial capacity contributes to skeletal muscle insulin resistance is debated. Our multifactorial analysis shows no differences in skeletal muscle mitochondrial content, mitochondrial capacity, and mitochondrial molecular profiles between obese individuals with and without T2D that had comparable levels of confounding factors (BMI, age, aerobic capacity). We highlight that lean, active individuals have enhanced skeletal muscle mitochondrial capacity that is also reflected at the level of DNA methylation and gene transcription.