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

Kana Oue, Jun Zhang, Kae Harada-Hada, Satoshi Asano, Yosuke Yamawaki, Masaki Hayashiuchi, Hisako Furusho, Takashi Takata, Masahiro Irifune, Masato Hirata, Takashi Kanematsu

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11 Citations (Scopus)

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 ther-moneutral 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.

Original languageEnglish
Pages (from-to)4185-4196
Number of pages12
JournalJournal of Biological Chemistry
Volume291
Issue number8
DOIs
Publication statusPublished - Feb 19 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Oue, K., Zhang, J., Harada-Hada, K., Asano, S., Yamawaki, Y., Hayashiuchi, M., Furusho, H., Takata, T., Irifune, M., Hirata, M., & Kanematsu, T. (2016). Phospholipase C-related Catalytically Inactive Protein Is a New Modulator of Thermogenesis Promoted by β-Adrenergic Receptors in Brown Adipocytes. Journal of Biological Chemistry, 291(8), 4185-4196. https://doi.org/10.1074/jbc.M115.705723