Effects of obesity and exercise training on mitochondrial function and insulin resistance in aging

초록

The objectives of this study were: (1) to determine the impacts of high fat diet-induced obesity on mitochondrial function and insulin resistance in aged skeletal muscle and (2) to determine the effects of exercise training on mitochondrial dysfunction and insulin resistance induced by obesity and aging in skeletal muscle. Sprague-Dawley rats were randomly divided into four groups: 4-month young control (YC), 20-month old control (OC), old high fat diet group (OH), 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 training was performed 6 times a week for 7 weeks. Mitochondrial function (e.g., H2O2 emission, Ca2+ retention capacity) was measured in permeabilized skeletal muscle (e.g., soleus, and white gastrocnemius), and oral glucose tolerance test (OGTT) and Western immunoblot analysis were performed to determine insulin resistance. Mitochondrial H2O2 emission was increased in white gastrocnemius (type IIb muscle) of OC and OH compared with YC. However, exercise training attenuated mitochondrial H2O2 emission in OH+EX compared with OC and OH. Mitochondrial Ca2+ retention capacity was not significantly altered between groups in soleus (type I muscle). However, in white gastrocnemius, mitochondrial Ca2+ retention capacity was reduced in OC and OH compared with YC and, conversely improved in OH+EX compared with OC and OH. Insulin resistance was also increased in OC and OH compared with YC. By contrast, insulin resistance was attenuated in OH+EX compared with OC and OH. In conclusion, our data reported that high fat diet increased mitochondrial H2O2 emission, reduced mitochondrial Ca2+ retention capacity, and induced insulin resistance in aged skeletal muscle. However, exercise training reduced mitochondrial H2O2 emission, improved mitochondrial Ca2+ retention capacity, and attenuated insulin resistance in aged and obese skeletal muscle, suggesting that e