Abstract
Obesity and aging reduce skeletal muscle contractile function. However, it remains unclear whether obesity additively promotes muscle contractile dysfunction in the setting of aging. In this study, we investigated skeletal muscle contractile function ex vivo and intracellular Ca2+ release in male C57BL/6J mice fed a low-fat diet (LFD) or a high-fat diet (HFD) for 4 or 20 mo. Tetanic force production in the extensor digitorum longus muscle was decreased by aging or HFD feeding, and the further reduction was observed in aged HFD mice. The 20-mo HFD-fed mice, not the 20-mo LFD-fed mice or 4-mo HFD-fed mice, showed reduced intracellular Ca2+ peak levels by high concentration of caffeine (25 mM) compared with 4-mo LFD mice. Aging and HFD feeding additively increased intramyocellular lipid (IMCL) levels and were associated with the degree of impaired muscle contractile force and peak Ca2+ level. These data suggest that impairment in the contractile force in aged muscle is aggravated by HFD, which may be due, at least in part, to dysfunction in intracellular Ca2+ release. The IMCL level may be a marker for impaired muscle contractile force caused by aging and HFD.NEW & NOTEWORTHY The aim of this study was to examine the effect of high-fat diet (HFD)-induced obesity on contractile function and Ca2+ release capacity in aged skeletal muscle. Not only were the force production and peak Ca2+ levels decreased by aging and HFD feeding, respectively, but also, these interventions had an additive effect in aged HFD-fed mice. These data suggest that the impairment in the contractile force in aged muscle is aggravated by a HFD, which may be due to synergistic dysfunction in intracellular Ca2+ release.