Abstract
Excessive fat accumulation has been considered as a major contributing factor for muscle mitochondrial dysfunction and its associated metabolic complications. The purpose of present study is to investigate a role of vitamin D in muscle fat accumulation and mitochondrial changes. In differentiated C2C12 muscle cells, palmitic acid (PA) was pretreated, followed by incubation with 1,25-dihyroxyvitamin D (1,25(OH)2D) for 24 h. PA led to a significant increment of triglyceride (TG) levels with increased lipid peroxidation and cellular damage, which were reversed by 1,25(OH)2D. The supplementation of 1,25(OH)2D significantly enhanced PA-decreased mtDNA levels as well as mRNA levels involved in mitochondrial biogenesis such as nuclear respiratory factor 1 (NRF1), peroxisome proliferative activated receptor gamma coactivator-1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in C2C12 myotubes. Additionally, 1,25(OH)2D significantly increased ATP levels and gene expression related to mitochondrial function such as carnitine palmitoyltransferase 1 (CPT1), peroxisome proliferator-activated receptor α (PPARα), very long-chain acyl-CoA dehydrogenase (VLCAD), long-chain acyl-CoA dehydrogenase (LCAD), medium-chain acyl-CoA dehydrogenase (MCAD), uncoupling protein 2 (UCP2), and UCP3 and the vitamin D pathway including 25-dihydroxyvitamin D3 24-hydroxylase (CYP24) and 25-hydroxyvitamin D3 1-alpha-hydroxylase (CYP27) in PA-treated C2C12 myotubes. In addition to significant increment of sirtuin 1 (SIRT1) mRNA expression, increased activation of adenosine monophosphate-activated protein kinase (AMPK) and SIRT1 was found in 1,25(OH)2D-treated C2C12 muscle cells. Thus, we suggest that the observed protective effect of vitamin D on muscle fat accumulation and mitochondrial dysfunction in a positive manner via modulating AMPK/SIRT1 activation.
Highlights
A chronic positive energy surplus leads to obesity, which is characterized by enlarged adipose tissue [1,2]
The effect of vitamin D status on muscle fat accumulation was examined by using HF diet with two vitamin D levels
Based on 1,25(OH)2Dof Mitochondrial DNA (mtDNA) and ATP, we suggest that increased vitamin D status might protect against palmitic acid (PA)-decreased increased levels of mtDNA and ATP, we suggest that increased vitamin D status might protect muscle mitochondrial changes
Summary
A chronic positive energy surplus leads to obesity, which is characterized by enlarged adipose tissue [1,2]. Reduced fat storage capacity in adipose tissue, in association with increased body fat mass, causes ectopic fat accumulation in muscle, liver, pancreas, and heart, which is the link between obesity and its associated metabolic disease such as insulin resistance, type 2 diabetes mellitus, and cardiovascular disease [3,4,5]. Skeletal muscle from obese humans show increased intramuscular triglyceride levels [6,7,8] and decreased mitochondrial contents and function [9]. It is important to regulate obesity-induced fat deposition and mitochondrial changes in skeletal muscle to prevent and/or treat obesity and its associated metabolic disorders. There is a close association between low vitamin D status and reduced muscle mass, Nutrients 2019, 11, 2806; doi:10.3390/nu11112806 www.mdpi.com/journal/nutrients
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