title: Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue.
abstract: Among the four prostaglandin E2 receptors, EP3 receptor is the one most abundantly expressed in white adipose tissue (WAT). The mouse EP3 gene gives rise to three isoforms, namely EP3α, EP3β, and EP3γ, which differ only at their C-terminal tails. To date, functions of EP3 receptor and its isoforms in WAT remain incompletely characterized. In this study, we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice. Genetic ablation of three EP3 receptor isoforms (EP3-/-mice) or EP3α and EP3γ isoforms with EP3β intact (EP3β mice) led to an obese phenotype with increased food intake, decreased motor activity, reduced insulin sensitivity, and elevated serum triglycerides. Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγ pathway, increased adipogenesis may contribute to obesity in EP3-/-and EP3β mice. Moreover, both EP3-/-and EP3β mice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway. Taken together, our findings suggest that EP3 receptor and its α and γ isoforms are involved in both adipogenesis and lipolysis and influence food intake, serum lipid levels, and insulin sensitivity.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jia-Lin
authors.initials: JL
authors.lastname: Fu
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Yi-Fei
authors.initials: YF
authors.lastname: Miao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Chun-Jiong
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Qi-Fei
authors.initials: QF
authors.lastname: Han
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Shi-Zheng
authors.initials: SZ
authors.lastname: Huang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Sheng-Nan
authors.initials: SN
authors.lastname: Du
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Qiu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Ji-Chun
authors.initials: JC
authors.lastname: Yang
authors.affiliation: Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA.
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Health Authority, and Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Breyer
authors.affiliation: Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Nan-Ping
authors.initials: NP
authors.lastname: Wang
authors.affiliation: Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China.|Department of Physiology, AstraZeneca-Shenzhen University Joint Institute of Nephrology, Shenzhen University Health Science Center, Shenzhen 518060, China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China guanyf@dmu.edu.cn.|Advanced Institute for Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: You-Fei
authors.initials: YF
authors.lastname: Guan
mesh_terms: D017667:Adipocytes / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis; D052436:Adipose Tissue, White / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D017353:Gene Deletion; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D008066:Lipolysis; D008079:Lipoproteins, VLDL / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D058308:Receptors, Prostaglandin E, EP3 Subtype / Q000378:metabolism*; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D008079:Lipoproteins, VLDL; D020033:Protein Isoforms; D058308:Receptors, Prostaglandin E, EP3 Subtype; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride
keywords: EP3 receptor isoform; PKA; PPARγ; arachidonic acid; insulin resistance; obesity