Calcitriol concomitantly enhances insulin sensitivity and alters myocellular lipid partitioning in high fat-treated skeletal muscle cells

Grace E. Jefferson, David M. Schnell, D. Travis Thomas, Lance M. Bollinger

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Vitamin D reduces myocellular insulin resistance, but the effects of vitamin D on intramyocellular lipid (IMCL) partitioning are unknown. The purpose of this study was to understand how calcitriol, the active vitamin D metabolite, affects insulin sensitivity and lipid partitioning in skeletal muscle cells. C2C12 myotubes were treated with calcitriol (100 nM) or vehicle control for 96 h. Insulin-stimulated Akt phosphorylation (Thr 308) was determined by western blot. Intramyocellular triacylglycerol (IMTG), diacylglycerol (DAG), and ceramide content were measured by LC/MS. IMTG partitioning and lipid droplet accumulation were assessed by oil red O. Expression of genes involved in lipid droplet packaging and lipolysis were measured by RT-PCR. Compared to vehicle-treated myotubes, calcitriol augmented insulin-stimulated pAkt. Calcitriol increased total ceramides and DAG in a subspecies-specific manner. Specifically, calcitriol preferentially increased ceramide 24:1 (1.78 fold) and di-18:0 DAG (46.89 fold). Calcitriol increased total IMTG area as assessed by oil red O, but decreased the proportion of lipid within myotubes. Calcitriol increased mRNA content of genes involved in lipid droplet packaging (perilipin 2; PLIN 2, 2.07 fold) and lipolysis (comparative gene identification-58; CGI-58 and adipose triglyceride lipase; ATGL, ~ 1.80 fold). Calcitriol alters myocellular lipid partitioning and lipid droplet packaging which may favor lipid turnover and partially explain improvements in insulin sensitivity.

Original languageEnglish
Pages (from-to)613-621
Number of pages9
JournalJournal of Physiology and Biochemistry
Volume73
Issue number4
DOIs
StatePublished - Nov 1 2017

Bibliographical note

Funding Information:
Author contributions GEJ participated in the experimental procedures, data analysis/interpretation, and manuscript writing. DMS helped in the data analysis/interpretation, manuscript writing/editing, and contributed intellectual contributions. DTT participated in the study design, data interpretation, manuscript review, and contributed financial support. LMB helped in the study design, experimental procedures, data analysis/ interpretation, manuscript writing, and contributed financial support.FundingThis study was funded in part by start-up funds from the University of Kentucky, College of Education (LMB) and NIH R21 AG046762 (DTT).

Publisher Copyright:
© 2017, University of Navarra.

Keywords

  • Insulin sensitivity
  • Intramyocellular lipid
  • Lipid droplet
  • Perilipin
  • Vitamin D

ASJC Scopus subject areas

  • Physiology
  • Biochemistry

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