Glycerol kinase stimulates uncoupling protein 1 expression by regulating fatty acid metabolism in beige adipocytes
| Autor: | Naoki Osato, Wataru Nomura, Takako Mukai, Haruya Takahashi, Huei-Fen Jheng, Shigeto Seno, Kazuo Inoue, Yu Sheng Yeh, Hideo Matsuda, Tatsuya Kusudo, Mari Iwase, Sigenobu Matsumura, Tsuyoshi Goto, Teruo Kawada, Soshi Tokiwa |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Transcriptional Activation Glycerol kinase Adipose tissue White adipose tissue Biochemistry Second Messenger Systems 03 medical and health sciences chemistry.chemical_compound Mice Adipocyte Glycerol Kinase Cyclic AMP Lipolysis Uncoupling protein Animals Adipocytes Beige Molecular Biology Uncoupling Protein 1 030102 biochemistry & molecular biology Fatty acid metabolism Fatty Acids Isoproterenol Thermogenesis Cell Biology Thermogenin Cell biology Cold Temperature 030104 developmental biology Metabolism chemistry Stearoyl-CoA Desaturase |
| Zdroj: | J Biol Chem |
| ISSN: | 1083-351X |
| Popis: | 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 β-adrenergic receptors (βAR) 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 βAR-cAMP-CREB pathway and Gyk-mediated regulation of fatty acid metabolism. |
| Databáze: | OpenAIRE |
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