| First Author | Hatting M | Year | 2017 |
| Journal | Cell Metab | Volume | 25 |
| Issue | 2 | Pages | 428-437 |
| PubMed ID | 28089567 | Mgi Jnum | J:251897 |
| Mgi Id | MGI:6107118 | Doi | 10.1016/j.cmet.2016.12.007 |
| Citation | Hatting M, et al. (2017) Adipose Tissue CLK2 Promotes Energy Expenditure during High-Fat Diet Intermittent Fasting. Cell Metab 25(2):428-437 |
| abstractText | 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. |
