Exercise Training Attenuates Sarcopenic Obesity‐Induced Insulin Resistance and Mitochondrial Dysfunction in the Rat Skeletal Muscle

Abstract

The purpose of this study was to determine the effects of sarcopenic obesity (aging‐induced sarcopenia plus high fat diet‐induced obesity) and exercise training on insulin resistance, mitochondrial function (hydrogen peroxide (H2O2) emission and calcium(Ca2+) retention capacity) and mitochondrial dynamics (fusion; Opa1, Mfn1, Mfn2 and fission; Drp1, Fis1) in the rat skeletal muscle.Sprague‐Dawley rats were randomly divided into four groups: 4‐month young control (YC), 20‐month old control (OC; sarcopenia), old high fat diet group (OH; sarcopenic obesity), and old high fat diet and exercise group (OH+EX). After obesity was induced by 7 weeks of 60% high fat feeding in old groups, treadmill exercise was performed 6 times a week for 7 weeks. Oral glucose tolerance test was performed to determine insulin resistance. Mitochondrial function (H2O2 emission, Ca2+ retention capacity) was measured in permeabilized skeletal muscle (soleus and white gastrocnemius). Also, mitochondrial dynamics (fusion and fission) were analyzed using Western immunoblot in skeletal muscle.Insulin resistance was induced in OC and OH compared with YC. Conversely, insulin resistance was mitigated in OH+EX compared with OC and OH. Excessive mitochondrial H2O2 emission was found in white gastrocnemius of OC and OH compared with YC. However, exercise training attenuated aging and obesity‐induced mitochondrial H2O2 emission in OH+EX compared with OC and OH. Although mitochondrial Ca2+ retention capacity was not significant between groups in type I muscle (soleus), it was dramatically downregulated by aging and obesity and conversely upregulated by exercise training in type IIb muscle (white gastrocnemius) in OH+EX compared with OC and OH. In addition, exercise training protected against the imbalance between mitochondrial fusion and fission, showing that aerobic exercise training improved aging and obesity (sarcopenic obesity)‐induced decrease in Opa1 and Mfn2 protein levels and, conversely, reduced the increase in Drp1 and Fis1 protein levels in type IIb muscle in OH+EX compared with OC and OH.Our data demonstrated that sarcopenic obesity induced more insulin resistance, mitochondrial dysfunction, and mitochondrial remodeling than sarcopenia in skeletal muscle. However, exercise training mitigated sarcopenic obesity‐induced impairment in insulin resistance and mitochondrial function in skeletal muscle, suggesting that aerobic exercise training plays an essential role in attenuating sarcopenic obesity‐induced insulin resistance through the regulation of mitochondrial function in the skeletal muscle.Support or Funding InformationThis work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation (2018R1A2A3074577, 2019S1A5C2A03082727).