Combined Effects of Treadmill Running and Vitamin D administration on Skeletal Muscle Morphology and Mitochondrial Dynamics in HFD-induced Obese Mice

PURPOSE The study aimed to investigate the effects of treadmill running and intraperitoneal vitamin D administration on the changes in skeletal muscle morphology and mitochondrial dynamics induced by a high-fat diet (HFD) in C57BL/6 mice. METHODS Fifty 5-week-old C57BL/6 mice were randomly assigned to either standard chow (SC, n=10) or HFD (n=40), and the ani-mals were maintained on each diet for 12 weeks. During the final 6 weeks on these diet, the HFD mice were further divided into four subgroups: HFD only (n=10), HFD plus treadmill running (HFD+EX, n=10), HFD plus vitamin D administration (HFD+VD, n=10), and HFD plus treadmill running plus vitamin D administration (HFD+VD+EX, n=10). The morphology and mitochondrial dynamics markers of the gastrocnemius were assessed with immunohistochemistry and western blot, respectively. RESULTS HFD resulted in morphological alterations in the muscle, such as decreased myocyte cross-sectional area and increased extramyocyte space. However, the HFD-induced morphological alterations were reversed by the combination of treadmill running and vitamin D administration (HFD vs. HFD+VD+EX). Furthermore, the combined treatment of treadmill running and vitamin D improved mitochondrial dynamics signaling pathways, such as mitochondrial fusion, fission, mitophagy, and mitochondria-mediated skeletal muscle apoptosis. CONCLUSIONS The findings of the study suggest that a combination of exercise and vitamin D supplementation might be an effective therapeutic strategy against HFD-induced morphological alterations and mitochondrial dysfunctions in skeletal muscle.