Back to Search Start Over

A Unique Role of Carboxylesterase 3 (Ces3) in β-Adrenergic Signaling-Stimulated Thermogenesis.

Authors :
Yang L
Li X
Tang H
Gao Z
Zhang K
Sun K
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.)

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