title: Phospholipase C-related Catalytically Inactive Protein Is a New Modulator of Thermogenesis Promoted by β-Adrenergic Receptors in Brown Adipocytes.
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.
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology, Dental Anesthesiology, and.
authors.forename: Kana
authors.initials: K
authors.lastname: Oue
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology.
authors.forename: Kae
authors.initials: K
authors.lastname: Harada-Hada
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asano
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamawaki
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hayashiuchi
authors.affiliation: Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553 and.
authors.forename: Hisako
authors.initials: H
authors.lastname: Furusho
authors.affiliation: Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553 and.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takata
authors.affiliation: Dental Anesthesiology, and.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Irifune
authors.affiliation: the Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Hirata
authors.affiliation: From the Departments of Cellular and Molecular Pharmacology, tkanema2@hiroshima-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kanematsu
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects / Q000494:pharmacology; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D022722:Thermogenesis; D000071256:Uncoupling Protein 1
chemical_list: D004041:Dietary Fats; D007473:Ion Channels; D024101:Mitochondrial Proteins; C405683:Ncoa6 protein, mouse; D056918:Nuclear Receptor Coactivators; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1
keywords: adipocyte; adipose tissue metabolism; lipolysis; obesity; thermogenesis; uncoupling protein