Phospholipase C-related Catalytically Inactive Protein Is a New Modulator of Thermogenesis Promoted by β-Adrenergic Receptors in Brown Adipocytes

J Biol Chem. 2016 Feb 19;291(8):4185-96. doi: 10.1074/jbc.M115.705723. Epub 2015 Dec 25.

Abstract

Phospholipase C-related catalytically inactive protein (PRIP) was first identified as an inositol 1,4,5-trisphosphate-binding protein, and was later found to be involved in a variety of cellular events, particularly those related to protein phosphatases. We previously reported that Prip knock-out (KO) mice exhibit a lean phenotype with a small amount of white adipose tissue. In the present study, we examined whether PRIP is involved in energy metabolism, which could explain the lean phenotype, using high-fat diet (HFD)-fed mice. Prip-KO mice showed resistance to HFD-induced obesity, resulting in protection from glucose metabolism dysfunction and insulin resistance. Energy expenditure and body temperature at night were significantly higher in Prip-KO mice than in wild-type mice. Gene and protein expression of uncoupling protein 1 (UCP1), a thermogenic protein, was up-regulated in Prip-KO brown adipocytes in thermoneutral or cold environments. These phenotypes were caused by the promotion of lipolysis in Prip-KO brown adipocytes, which is triggered by up-regulation of phosphorylation of the lipolysis-related proteins hormone-sensitive lipase and perilipin, followed by activation of UCP1 and/or up-regulation of thermogenesis-related genes (e.g. peroxisome proliferator-activated receptor-γ coactivator-1α). The results indicate that PRIP negatively regulates UCP1-mediated thermogenesis in brown adipocytes.

Keywords: adipocyte; adipose tissue metabolism; lipolysis; obesity; thermogenesis; uncoupling protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Brown / metabolism*
  • Adipocytes, Brown / pathology
  • Animals
  • Dietary Fats / adverse effects
  • Dietary Fats / pharmacology
  • Ion Channels / genetics
  • Ion Channels / metabolism*
  • Lipolysis*
  • Mice
  • Mice, Knockout
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism*
  • Nuclear Receptor Coactivators / genetics
  • Nuclear Receptor Coactivators / metabolism*
  • Obesity / chemically induced
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / pathology
  • Thermogenesis*
  • Uncoupling Protein 1

Substances

  • Dietary Fats
  • Ion Channels
  • Mitochondrial Proteins
  • Ncoa6 protein, mouse
  • Nuclear Receptor Coactivators
  • Ucp1 protein, mouse
  • Uncoupling Protein 1