First Author | Oue K | Year | 2016 |
Journal | J Biol Chem | Volume | 291 |
Issue | 8 | Pages | 4185-96 |
PubMed ID | 26706316 | Mgi Jnum | J:231034 |
Mgi Id | MGI:5766689 | Doi | 10.1074/jbc.M115.705723 |
Citation | Oue K, et al. (2016) Phospholipase C-related Catalytically Inactive Protein Is a New Modulator of Thermogenesis Promoted by beta-Adrenergic Receptors in Brown Adipocytes. J Biol Chem 291(8):4185-96 |
abstractText | 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-gamma coactivator-1alpha). The results indicate that PRIP negatively regulates UCP1-mediated thermogenesis in brown adipocytes. |