Journal
CELL METABOLISM
Volume 25, Issue 2, Pages 428-437Publisher
CELL PRESS
DOI: 10.1016/j.cmet.2016.12.007
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Funding
- Deutsche Forschungsgemeinschaft (DFG) [HA 7246/1-1]
- Medizinische Fakultat
- RWTH Aachen University
- Rotationstellenprogramm
- National Institute of Diabetes and Digestive and Kidney Diseases [NRSA F32 DK102293-03]
- DFG [TR 285/10-1]
- American Diabetes Association
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases [1-R01-DK-089883-01A1]
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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.
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