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

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)997-1008
Number of pages12
JournalCell metabolism
Volume22
Issue number6
DOIs
StatePublished - 2015

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Shinoda, K., Ohyama, K., Hasegawa, Y., Chang, H. Y., Ogura, M., Sato, A., Hong, H., Hosono, T., Sharp, L. Z., Scheel, D. W., Graham, M., Ishihama, Y., & Kajimura, S. (2015). Phosphoproteomics Identifies CK2 as a Negative Regulator of Beige Adipocyte Thermogenesis and Energy Expenditure. Cell metabolism, 22(6), 997-1008. https://doi.org/10.1016/j.cmet.2015.09.029