PMID- 32273338 OWN - NLM STAT- MEDLINE DCOM- 20201223 LR - 20210516 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 295 IP - 20 DP - 2020 May 15 TI - Glycerol kinase stimulates uncoupling protein 1 expression by regulating fatty acid metabolism in beige adipocytes. PG - 7033-7045 LID - 10.1074/jbc.RA119.011658 [doi] AB - Browning of adipose tissue is induced by specific stimuli such as cold exposure and consists of up-regulation of thermogenesis in white adipose tissue. Recently, it has emerged as an attractive target for managing obesity in humans. Here, we performed a comprehensive analysis to identify genes associated with browning in murine adipose tissue. We focused on glycerol kinase (GYK) because its mRNA expression pattern is highly correlated with that of uncoupling protein 1 (UCP1), which regulates the thermogenic capacity of adipocytes. Cold exposure-induced Ucp1 up-regulation in inguinal white adipose tissue (iWAT) was partially abolished by Gyk knockdown (KD) in vivo Consistently, the Gyk KD inhibited Ucp1 expression induced by treatment with the beta-adrenergic receptors (betaAR) agonist isoproterenol (Iso) in vitro and resulted in impaired uncoupled respiration. Gyk KD also suppressed Iso- and adenylate cyclase activator-induced transcriptional activation and phosphorylation of the cAMP response element-binding protein (CREB). However, we did not observe these effects with a cAMP analog. Therefore Gyk KD related to Iso-induced cAMP products. In Iso-treated Gyk KD adipocytes, stearoyl-CoA desaturase 1 (SCD1) was up-regulated, and monounsaturated fatty acids such as palmitoleic acid (POA) accumulated. Moreover, a SCD1 inhibitor treatment recovered the Gyk KD-induced Ucp1 down-regulation and POA treatment down-regulated Iso-activated Ucp1 Our findings suggest that Gyk stimulates Ucp1 expression via a mechanism that partially depends on the betaAR-cAMP-CREB pathway and Gyk-mediated regulation of fatty acid metabolism. CI - (c) 2020 Iwase et al. FAU - Iwase, Mari AU - Iwase M AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Tokiwa, Soshi AU - Tokiwa S AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Seno, Shigeto AU - Seno S AD - Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita 565-0871, Japan. FAU - Mukai, Takako AU - Mukai T AD - Faculty of Human Sciences, Tezukayama Gakuin University, Sakai 590-0113, Japan. FAU - Yeh, Yu-Sheng AU - Yeh YS AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Takahashi, Haruya AU - Takahashi H AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Nomura, Wataru AU - Nomura W AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. AD - Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8317, Japan. FAU - Jheng, Huei-Fen AU - Jheng HF AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Matsumura, Sigenobu AU - Matsumura S AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Kusudo, Tatsuya AU - Kusudo T AD - Faculty of Human Sciences, Tezukayama Gakuin University, Sakai 590-0113, Japan. FAU - Osato, Naoki AU - Osato N AD - Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita 565-0871, Japan. FAU - Matsuda, Hideo AU - Matsuda H AUID- ORCID: 0000-0002-4701-3779 AD - Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, Suita 565-0871, Japan. FAU - Inoue, Kazuo AU - Inoue K AUID- ORCID: 0000-0001-7003-8635 AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. FAU - Kawada, Teruo AU - Kawada T AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan. AD - Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8317, Japan. FAU - Goto, Tsuyoshi AU - Goto T AUID- ORCID: 0000-0003-1283-147X AD - Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji, Kyoto 611-0011, Japan goto.tsuyoshi.6x@kyoto-u.ac.jp. AD - Research Unit for Physiological Chemistry, Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8317, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200409 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Fatty Acids) RN - 0 (Ucp1 protein, mouse) RN - 0 (Uncoupling Protein 1) RN - E0399OZS9N (Cyclic AMP) RN - EC 1.14.19.1 (Scd1 protein, mouse) RN - EC 1.14.19.1 (Stearoyl-CoA Desaturase) RN - EC 2.7.1.30 (Glycerol Kinase) RN - L628TT009W (Isoproterenol) SB - IM MH - Adipocytes, Beige/cytology/*metabolism MH - Animals MH - *Cold Temperature MH - Cyclic AMP/genetics/metabolism MH - Fatty Acids/genetics/*metabolism MH - Glycerol Kinase/genetics/*metabolism MH - Isoproterenol/pharmacology MH - Male MH - Mice MH - *Second Messenger Systems MH - Stearoyl-CoA Desaturase/genetics/metabolism MH - *Thermogenesis MH - *Transcriptional Activation MH - Uncoupling Protein 1/*biosynthesis/genetics PMC - PMC7242690 OTO - NOTNLM OT - adipocyte OT - adipose tissue OT - fatty acid OT - fatty acid metabolism OT - lipogenesis OT - lipolysis OT - obesity OT - thermogenesis OT - uncoupling protein COIS- The authors declare that they have no conflicts of interest with the contents of this article EDAT- 2020/04/11 06:00 MHDA- 2020/12/29 06:00 PMCR- 2021/05/15 CRDT- 2020/04/11 06:00 PHST- 2019/10/29 00:00 [received] PHST- 2020/04/02 00:00 [revised] PHST- 2020/04/11 06:00 [pubmed] PHST- 2020/12/29 06:00 [medline] PHST- 2020/04/11 06:00 [entrez] PHST- 2021/05/15 00:00 [pmc-release] AID - S0021-9258(17)48206-8 [pii] AID - RA119.011658 [pii] AID - 10.1074/jbc.RA119.011658 [doi] PST - ppublish SO - J Biol Chem. 2020 May 15;295(20):7033-7045. doi: 10.1074/jbc.RA119.011658. Epub 2020 Apr 9.