PMID- 33796846 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210403 IS - 2589-0042 (Electronic) IS - 2589-0042 (Linking) VI - 24 IP - 4 DP - 2021 Apr 23 TI - GPR52 accelerates fatty acid biosynthesis in a ligand-dependent manner in hepatocytes and in response to excessive fat intake in mice. PG - 102260 LID - 10.1016/j.isci.2021.102260 [doi] LID - 102260 AB - Gpr52 is an orphan G-protein-coupled receptor of unknown physiological function. We found that Gpr52-deficient (Gpr52 (-/-) ) mice exhibit leanness associated with reduced liver weight, decreased hepatic de novo lipogenesis, and enhanced insulin sensitivity. Treatment of the hepatoma cell line HepG2 cells with c11, the synthetic GPR52 agonist, increased fatty acid biosynthesis, and GPR52 knockdown (KD) abolished the lipogenic action of c11. In addition, c11 induced the expressions of lipogenic enzymes (SCD1 and ELOVL6), whereas these inductions were attenuated by GPR52-KD. In contrast, cholesterol biosynthesis was not increased by c11, but its basal level was significantly suppressed by GPR52-KD. High-fat diet (HFD)-induced increase in hepatic expression of Pparg2 and its targets (Scd1 and Elovl6) was absent in Gpr52 (-/-) mice with alleviated hepatosteatosis. Our present study showed that hepatic GPR52 promotes the biosynthesis of fatty acid and cholesterol in a ligand-dependent and a constitutive manner, respectively, and Gpr52 participates in HFD-induced fatty acid synthesis in liver. CI - (c) 2021 The Authors. FAU - Wada, Mitsuo AU - Wada M AD - Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan. AD - Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan. FAU - Yukawa, Kayo AU - Yukawa K AD - Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan. FAU - Ogasawara, Hiroyuki AU - Ogasawara H AD - Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan. FAU - Suzawa, Koichi AU - Suzawa K AD - Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki 569-1125, Japan. FAU - Maekawa, Tatsuya AU - Maekawa T AD - Central Pharmaceutical Research Institute, Japan Tobacco Inc., Takatsuki 569-1125, Japan. FAU - Yamamoto, Yoshihisa AU - Yamamoto Y AD - Pharmaceutical Frontier Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., Yokohama 236-0004, Japan. FAU - Ohta, Takeshi AU - Ohta T AD - Laboratory of Animal Physiology and Functional Anatomy, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan. FAU - Lee, Eunyoung AU - Lee E AD - Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan. FAU - Miki, Takashi AU - Miki T AD - Department of Medical Physiology, Chiba University, Graduate School of Medicine, Chiba 260-8670, Japan. LA - eng PT - Journal Article DEP - 20210302 PL - United States TA - iScience JT - iScience JID - 101724038 PMC - PMC7995607 OTO - NOTNLM OT - Human Metabolism OT - Molecular Biology COIS- The authors declare no competing interests. EDAT- 2021/04/03 06:00 MHDA- 2021/04/03 06:01 PMCR- 2021/03/02 CRDT- 2021/04/02 06:39 PHST- 2020/11/09 00:00 [received] PHST- 2021/02/06 00:00 [revised] PHST- 2021/02/26 00:00 [accepted] PHST- 2021/04/02 06:39 [entrez] PHST- 2021/04/03 06:00 [pubmed] PHST- 2021/04/03 06:01 [medline] PHST- 2021/03/02 00:00 [pmc-release] AID - S2589-0042(21)00228-5 [pii] AID - 102260 [pii] AID - 10.1016/j.isci.2021.102260 [doi] PST - epublish SO - iScience. 2021 Mar 2;24(4):102260. doi: 10.1016/j.isci.2021.102260. eCollection 2021 Apr 23.