Perilipin 5 fine-tunes lipid oxidation to metabolic demand and protects against lipotoxicity in skeletal muscle

Sci Rep. 2016 Dec 6:6:38310. doi: 10.1038/srep38310.


Lipid droplets (LD) play a central role in lipid homeostasis by controlling transient fatty acid (FA) storage and release from triacylglycerols stores, while preventing high levels of cellular toxic lipids. This crucial function in oxidative tissues is altered in obesity and type 2 diabetes. Perilipin 5 (PLIN5) is a LD protein whose mechanistic and causal link with lipotoxicity and insulin resistance has raised controversies. We investigated here the physiological role of PLIN5 in skeletal muscle upon various metabolic challenges. We show that PLIN5 protein is elevated in endurance-trained (ET) subjects and correlates with muscle oxidative capacity and whole-body insulin sensitivity. When overexpressed in human skeletal muscle cells to recapitulate the ET phenotype, PLIN5 diminishes lipolysis and FA oxidation under basal condition, but paradoxically enhances FA oxidation during forskolin- and contraction- mediated lipolysis. Moreover, PLIN5 partly protects muscle cells against lipid-induced lipotoxicity. In addition, we demonstrate that down-regulation of PLIN5 in skeletal muscle inhibits insulin-mediated glucose uptake under normal chow feeding condition, while paradoxically improving insulin sensitivity upon high-fat feeding. These data highlight a key role of PLIN5 in LD function, first by finely adjusting LD FA supply to mitochondrial oxidation, and second acting as a protective factor against lipotoxicity in skeletal muscle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Weight
  • Diglycerides / metabolism
  • Gene Expression
  • Humans
  • Insulin Resistance
  • Lipid Droplets / chemistry
  • Lipid Droplets / drug effects
  • Lipid Droplets / metabolism*
  • Lipolysis / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Oleic Acid / metabolism
  • Oleic Acid / pharmacology
  • Oxidation-Reduction
  • Perilipin-5 / genetics*
  • Perilipin-5 / metabolism
  • Physical Endurance / physiology
  • Primary Cell Culture
  • Satellite Cells, Skeletal Muscle / cytology
  • Satellite Cells, Skeletal Muscle / drug effects
  • Satellite Cells, Skeletal Muscle / metabolism*
  • Sedentary Behavior
  • Triglycerides / metabolism


  • Diglycerides
  • PLIN5 protein, human
  • Perilipin-5
  • Plin5 protein, mouse
  • Triglycerides
  • Oleic Acid

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