A Unique Role of Carboxylesterase 3 (Ces3) in β-Adrenergic Signaling–Stimulated Thermogenesis
| Autor: | Kangling Zhang, Hui Tang, Kai Sun, Li Yang, Xin Li, Zhanguo Gao |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Lipolysis Endocrinology Diabetes and Metabolism Down-Regulation Adipose tissue 030209 endocrinology & metabolism Carboxylesterase Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation In vivo 3T3-L1 Cells Lipid droplet Internal Medicine Animals RNA Small Interfering Carboxylesterase 3 Receptor Uncoupling Protein 1 Mice Knockout Chemistry Isoproterenol Thermogenesis Adrenergic beta-Agonists Peroxisome Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria Cell biology Cold Temperature PPAR gamma Adipocytes Brown 030104 developmental biology Adipose Tissue Obesity Studies |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db18-1210 |
| Popis: | 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 β-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 Pgc1α genes via peroxisome proliferator–activated receptor γ. 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-Ces3flx/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. |
| Databáze: | OpenAIRE |
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