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 animals 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.