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Vitamin D produces a perilipin 2-dependent increase in mitochondrial function in C2C12 myotubes.

TitleVitamin D produces a perilipin 2-dependent increase in mitochondrial function in C2C12 myotubes.
Publication TypeJournal Article
Year of Publication2019
AuthorsSchnell DM, R Walton G, Vekaria HJ, Sullivan PG, Bollinger LM, Peterson CA, D Thomas T
JournalJ Nutr Biochem
Date Published2019 03
KeywordsAnimals, Calcitriol, Cell Line, Diacylglycerol O-Acyltransferase, Gene Expression Regulation, Gene Knockdown Techniques, Lipid Metabolism, Mice, Mitochondria, Muscle, Muscle Fibers, Skeletal, Perilipin-2, Vitamin D

Vitamin D has been connected with increased intramyocellular lipid (IMCL) and has also been shown to increase mitochondrial function and insulin sensitivity. Evidence suggests that perilipin 2 (PLIN2), a perilipin protein upregulated with calcitriol treatment, may be integral to managing increased IMCL capacity and lipid oxidation in skeletal muscle. Therefore, we hypothesized that PLIN2 is required for vitamin D induced IMCL accumulation and increased mitochondrial oxidative function. To address this hypothesis, we treated C2C12 myotubes with 100 nM calcitriol (the active form of vitamin D) and/or PLIN2 siRNA in a four group design and analyzed markers of IMCL accumulation and metabolism using qRT-PCR, cytochemistry, and oxygen consumption assay. Expression of PLIN2, but not PLIN3 or PLIN5 mRNA was increased with calcitriol, and PLIN2 induction was prevented with siRNA knockdown without compensation by other perilipins. PLIN2 knockdown did not appear to prevent lipid accumulation. Calcitriol treatment increased mRNA expression of triglyceride synthesizing genes DGAT1 and DGAT2 and also lipolytic genes ATGL and CGI-58. PLIN2 knockdown decreased the expression of CGI-58 and CPT1, and was required for calcitriol-induced upregulation of DGAT2. Calcitriol increased oxygen consumption rate while PLIN2 knockdown decreased oxygen consumption rate. PLIN2 was required for a calcitriol-induced increase in oxygen consumption driven by mitochondrial complex II. We conclude that calcitriol increases mitochondrial function in myotubes and that this increase is at least in part mediated by PLIN2.

Alternate JournalJ. Nutr. Biochem.
PubMed ID30658160
PubMed Central IDPMC6420373
Grant ListP20 GM121327 / GM / NIGMS NIH HHS / United States
R21 AG046762 / AG / NIA NIH HHS / United States
T32 DK007778 / DK / NIDDK NIH HHS / United States