The G0/G1 Switch Gene 2 Regulates Adipose Lipolysis through Association with Adipose Triglyceride Lipase

Xingyuan Yang; Xin Lu; Marc Lombès; Geun Bae Rha; Young In Chi; Theresa M. Guerin; Eric J. Smart; Jun Liu

doi:10.1016/j.cmet.2010.02.003

The G₀/G₁ Switch Gene 2 Regulates Adipose Lipolysis through Association with Adipose Triglyceride Lipase

Xingyuan Yang, Xin Lu, Marc Lombès, Geun Bae Rha, Young In Chi, Theresa M. Guerin, Eric J. Smart, Jun Liu

Research output: Contribution to journal › Article › peer-review

354 Scopus citations

Abstract

Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G₀/G₁ switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.

Original language	English (US)
Pages (from-to)	194-205
Number of pages	12
Journal	Cell Metabolism
Volume	11
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2010.02.003
State	Published - Mar 3 2010
Externally published	Yes

Bibliographical note

Funding Information:
We thank Drs. Carole Sztalryd, Matthew J. Brady, Xiaowei Chen, Alan Cheng, and William V. Everson for reviewing the manuscript and helpful discussions. We also thank Dr. Say Viengchareun for excellent technical advice. The work was supported by a NIH grant DK 078742 and a Center of Biomedical Research Excellence pilot grant from the University of Kentucky (5P20 RR0202171) to J.L. and NIH grants RR015592 and DK077632 to E.J.S.

Keywords

HUMDISEASE

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10.1016/j.cmet.2010.02.003

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title = "The G0/G1 Switch Gene 2 Regulates Adipose Lipolysis through Association with Adipose Triglyceride Lipase",

abstract = "Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G0/G1 switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.",

keywords = "HUMDISEASE",

author = "Xingyuan Yang and Xin Lu and Marc Lomb{\`e}s and Rha, {Geun Bae} and Chi, {Young In} and Guerin, {Theresa M.} and Smart, {Eric J.} and Jun Liu",

note = "Funding Information: We thank Drs. Carole Sztalryd, Matthew J. Brady, Xiaowei Chen, Alan Cheng, and William V. Everson for reviewing the manuscript and helpful discussions. We also thank Dr. Say Viengchareun for excellent technical advice. The work was supported by a NIH grant DK 078742 and a Center of Biomedical Research Excellence pilot grant from the University of Kentucky (5P20 RR0202171) to J.L. and NIH grants RR015592 and DK077632 to E.J.S. ",

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T1 - The G0/G1 Switch Gene 2 Regulates Adipose Lipolysis through Association with Adipose Triglyceride Lipase

AU - Yang, Xingyuan

AU - Lu, Xin

AU - Lombès, Marc

AU - Rha, Geun Bae

AU - Chi, Young In

AU - Guerin, Theresa M.

AU - Smart, Eric J.

AU - Liu, Jun

N1 - Funding Information: We thank Drs. Carole Sztalryd, Matthew J. Brady, Xiaowei Chen, Alan Cheng, and William V. Everson for reviewing the manuscript and helpful discussions. We also thank Dr. Say Viengchareun for excellent technical advice. The work was supported by a NIH grant DK 078742 and a Center of Biomedical Research Excellence pilot grant from the University of Kentucky (5P20 RR0202171) to J.L. and NIH grants RR015592 and DK077632 to E.J.S.

PY - 2010/3/3

Y1 - 2010/3/3

N2 - Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G0/G1 switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.

AB - Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G0/G1 switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis.

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