Phosphoproteomics Identifies CK2 as a Negative Regulator of Beige Adipocyte Thermogenesis and Energy Expenditure

Kosaku Shinoda, Kana Ohyama, Yutaka Hasegawa, Hsin Yi Chang, Mayu Ogura, Ayaka Sato, Haemin Hong, Takashi Hosono, Louis Z. Sharp, David W. Scheel, Mark Graham, Yasushi Ishihama, Shingo Kajimura

研究成果: 雜誌貢獻文章

39 引文 斯高帕斯(Scopus)

摘要

Catecholamines promote lipolysis both in brown and white adipocytes, whereas the same stimuli preferentially activate thermogenesis in brown adipocytes. Molecular mechanisms for the adipose-selective activation of thermogenesis remain poorly understood. Here, we employed quantitative phosphoproteomics to map global and temporal phosphorylation profiles in brown, beige, and white adipocytes under β3-adrenenoceptor activation and identified kinases responsible for the adipose-selective phosphorylation profiles. We found that casein kinase2 (CK2) activity is preferentially higher in white adipocytes than brown/beige adipocytes. Genetic or pharmacological blockade of CK2 in white adipocytes activates the thermogenic program in response to cAMP stimuli. Such activation is largely through reduced CK2-mediated phosphorylation of class I HDACs. Notably, inhibition of CK2 promotes beige adipocyte biogenesis and leads to an increase in whole-body energy expenditure and ameliorates diet-induced obesity and insulin resistance. These results indicate that CK2 is a plausible target to rewire the β3-adrenenoceptor signaling cascade that promotes thermogenesis in adipocytes.
原文英語
頁(從 - 到)997-1008
頁數12
期刊Cell Metabolism
22
發行號6
DOIs
出版狀態已發佈 - 一月 1 2015
對外發佈Yes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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