| First Author | Yang L | Year | 2019 |
| Journal | Diabetes | Volume | 68 |
| Issue | 6 | Pages | 1178-1196 |
| PubMed ID | 30862682 | Mgi Jnum | J:276211 |
| Mgi Id | MGI:6306193 | Doi | 10.2337/db18-1210 |
| Citation | Yang L, et al. (2019) A Unique Role of Carboxylesterase 3 (Ces3) in beta-Adrenergic Signaling-Stimulated Thermogenesis. Diabetes 68(6):1178-1196 |
| abstractText | Carboxylesterase 3 (Ces3) is a hydrolase with a wide range of activities in liver and adipose tissue. In this study, we identified Ces3 as a major lipid droplet surface-targeting protein in adipose tissue upon cold exposure by liquid chromatography-tandem mass spectrometry. To investigate the function of Ces3 in the beta-adrenergic signaling-activated adipocytes, we applied WWL229, a specific Ces3 inhibitor, or genetic inhibition by siRNA to Ces3 on isoproterenol (ISO)-treated 3T3-L1 and brown adipocyte cells. We found that blockage of Ces3 by WWL229 or siRNA dramatically attenuated the ISO-induced lipolytic effect in the cells. Furthermore, Ces3 inhibition led to impaired mitochondrial function measured by Seahorse. Interestingly, Ces3 inhibition attenuated an ISO-induced thermogenic program in adipocytes by downregulating Ucp1 and Pgc1alpha genes via peroxisome proliferator-activated receptor gamma. We further confirmed the effects of Ces3 inhibition in vivo by showing that the thermogenesis in adipose tissues was significantly attenuated in WWL229-treated or adipose tissue-specific Ces3 heterozygous knockout (Adn-Cre-Ces3(flx/wt)) mice. As a result, the mice exhibited dramatically impaired ability to defend their body temperature in coldness. In conclusion, our study highlights a lipolytic signaling induced by Ces3 as a unique process to regulate thermogenesis in adipose tissue. |
