JPOST Repositoryapplication/xmlhttps://storage.jpostdb.org/JPST001719/files/rawfiles.txthttps://storage.jpostdb.org/JPST001719/files/150528aki_ing20.maxq.txthttps://storage.jpostdb.org/JPST001719/files/150528aki_ing20.txtprimaryOK200ProteomicsYasushi IshihamaMus Musculus (mouse)https://repository.jpostdb.org/entry/JPST001719jPOSTjPOSTfalseJPST000091-4 White adipocyte phosphoproteomics [Reanalysis: JPST000091]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 project description]Sat Mar 11 00:00:00 GMT 2023RPXD03472210090