| Literature DB >> 28089567 |
Maximilian Hatting1, Amy K Rines2, Chi Luo2, Mitsuhisa Tabata2, Kfir Sharabi2, Jessica A Hall2, Francisco Verdeguer2, Christian Trautwein3, Pere Puigserver4.
Abstract
A promising approach to treating obesity is to increase diet-induced thermogenesis in brown adipose tissue (BAT), but the regulation of this process remains unclear. Here we find that CDC-like kinase 2 (CLK2) is expressed in BAT and upregulated upon refeeding. Mice lacking CLK2 in adipose tissue exhibit exacerbated obesity and decreased energy expenditure during high-fat diet intermittent fasting. Additionally, tissue oxygen consumption and protein levels of UCP1 are reduced in CLK2-deficient BAT. Phosphorylation of CREB, a transcriptional activator of UCP1, is markedly decreased in BAT cells lacking CLK2 due to enhanced CREB dephosphorylation. Mechanistically, CREB dephosphorylation is rescued by the inhibition of PP2A, a phosphatase that targets CREB. Our results suggest that CLK2 is a regulatory component of diet-induced thermogenesis in BAT through increased CREB-dependent expression of UCP1.Entities:
Keywords: CLK2; PP2A; UCP1; brown fat; diet-induced thermogenesis; high-fat diet; intermittent fasting; p-CREB; refeeding
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Year: 2017 PMID： 28089567 PMCID： PMC5299049 DOI： 10.1016/j.cmet.2016.12.007
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287