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A Unique Role of Carboxylesterase 3 (Ces3) in β-Adrenergic Signaling-Stimulated Thermogenesis.
- Source :
-
Diabetes [Diabetes] 2019 Jun; Vol. 68 (6), pp. 1178-1196. Date of Electronic Publication: 2019 Mar 12. - Publication Year :
- 2019
-
Abstract
- 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-Ces3 <superscript>flx/wt</superscript> ) 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.<br /> (© 2019 by the American Diabetes Association.)
- Subjects :
- 3T3-L1 Cells
Adipocytes, Brown drug effects
Adipose Tissue drug effects
Adrenergic beta-Agonists pharmacology
Animals
Carboxylesterase antagonists & inhibitors
Carboxylesterase genetics
Cold Temperature
Down-Regulation
Isoproterenol pharmacology
Lipolysis drug effects
Mice
Mice, Knockout
Mitochondria drug effects
Mitochondria metabolism
PPAR gamma metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha genetics
RNA, Small Interfering
Thermogenesis drug effects
Uncoupling Protein 1 genetics
Adipocytes, Brown metabolism
Adipose Tissue metabolism
Carboxylesterase physiology
Lipolysis genetics
Thermogenesis genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1939-327X
- Volume :
- 68
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Diabetes
- Publication Type :
- Academic Journal
- Accession number :
- 30862682
- Full Text :
- https://doi.org/10.2337/db18-1210