Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity.

M. Bosma, L.M. Sparks, G. Hooiveld, J. Jorgensen, S.M. Houten, P. Schrauwen, S. Kersten, M.K.C. Hesselink

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Aims/hypothesis While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression - in comparison with effects of PLIN2 - on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. METHODS: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. RESULTS: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPARalpha and PGC1alpha involved in FA catabolism and mitochondrial oxidation.
Original languageEnglish
Pages (from-to)844-852
Number of pages9
JournalBiochimica et Biophysica Acta-Molecular and Cell Biology of Lipids
Volume1831
Issue number4
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Lipid droplet
  • Perilipin
  • OXPAT
  • Skeletal muscle
  • Insulin sensitivity
  • Oxidative gene expression
  • FATTY-ACID OXIDATION
  • PERILIPIN 5
  • WEIGHT-LOSS
  • PPAR-ALPHA
  • IN-VIVO
  • RESISTANCE
  • PROTEIN
  • MITOCHONDRIA
  • CARNITINE
  • PHOSPHORYLATION

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