title: PKA-RIIB Deficiency Induces Brown Fatlike Adipocytes in Inguinal WAT and Promotes Energy Expenditure in Male FVB/NJ Mice.
abstract: Obesity has become the most common metabolic disorder worldwide. Promoting brown adipose tissue (BAT) and beige adipose tissue formation, and therefore, a functional increase in energy expenditure, may counteract obesity. Mice lacking type IIβ regulatory subunit of adenosine 3',5' cyclic monophosphate (cAMP)-dependent protein kinase A (PKA-RIIB) display reduced adiposity and resistance to diet-induced obesity. PKA-RIIB, encoded by the Prkar2b gene, is most abundant in BAT and white adipose tissue (WAT) and in the brain. In this study, we show that mice lacking PKA-RIIB have increased energy expenditure, limited weight gain, and improved glucose metabolism. PKA-RIIB deficiency induces brownlike adipocyte in inguinal WAT (iWAT). PKA-RIIB deficiency also increases the expression of uncoupling protein 1 and other thermogenic genes in iWAT and primary preadipocytes from iWAT through a mechanism involving increased PKA activity, which is represented by increased phosphorylation of PKA substrate, cAMP response element binding protein, and P38 mitogen-activated protein kinase. Our study provides evidence for the role of PKA-RIIB deficiency in regulating thermogenesis in WAT, which may potentially have therapeutic implications for the treatment of obesity and related metabolic disorders.
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Ruidan
authors.initials: R
authors.lastname: Xue
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Lv
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Qiongyue
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Zhaoyun
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Ye
authors.affiliation: Institute of Developmental Biology and Molecular Medicine, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Endocrinology and Metabolism, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
mesh_terms: D052437:Adipocytes, Brown; D052436:Adipose Tissue, White / Q000166:cytology*; D000818:Animals; D050260:Carbohydrate Metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / Q000172:deficiency*; D004734:Energy Metabolism; D004822:Epididymis / Q000166:cytology; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D009765:Obesity / Q000378:metabolism; D022722:Thermogenesis; D000071256:Uncoupling Protein 1 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose