Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype

Maryam Ahmadian; Marcia J. Abbott; Tianyi Tang; Carolyn S.S. Hudak; Yangha Kim; Matthew Bruss; Marc K. Hellerstein; Hui Young Lee; Varman T. Samuel; Gerald I. Shulman; Yuhui Wang; Robin E. Duncan; Chulho Kang; Hei Sook Sul

doi:10.1016/j.cmet.2011.05.002

Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype

Maryam Ahmadian, Marcia J. Abbott, Tianyi Tang, Carolyn S.S. Hudak, Yangha Kim, Matthew Bruss, Marc K. Hellerstein, Hui Young Lee, Varman T. Samuel, Gerald I. Shulman, Yuhui Wang, Robin E. Duncan, Chulho Kang, Hei Sook Sul

Department of Nutritional Science & Food Management

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

416 Scopus citations

Abstract

While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated by AMPK at S406, increasing TAG hydrolase activity, and provide evidence for increased lipolysis by AMPK phosphorylation of desnutrin in adipocytes and in vivo. Despite adiposity and impaired BAT function, desnutrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis.

Original language	English
Pages (from-to)	739-748
Number of pages	10
Journal	Cell Metabolism
Volume	13
Issue number	6
DOIs	https://doi.org/10.1016/j.cmet.2011.05.002
State	Published - 8 Jun 2011

Bibliographical note

Funding Information:
This work was supported in part by DK75682 (H.S.S.), DK40936 (G.I.S.), and U24 DK076169 (V.T.S. and G.I.S.) from the National Institutes of Health. The authors thank R. Wong, A. Thompson, G. Wong, T. Liu, R. Mantara, T. Voortman, and E. Morse for technical and graphical assistance; A. Stahl and M. Kazantzis for help in metabolic chamber experiments; and A. Bradley for providing the pFlexible plasmid.

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10.1016/j.cmet.2011.05.002

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@article{02f538fb66ba4b3ca38b3f487898391e,

title = "Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype",

abstract = "While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated by AMPK at S406, increasing TAG hydrolase activity, and provide evidence for increased lipolysis by AMPK phosphorylation of desnutrin in adipocytes and in vivo. Despite adiposity and impaired BAT function, desnutrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis.",

author = "Maryam Ahmadian and Abbott, {Marcia J.} and Tianyi Tang and Hudak, {Carolyn S.S.} and Yangha Kim and Matthew Bruss and Hellerstein, {Marc K.} and Lee, {Hui Young} and Samuel, {Varman T.} and Shulman, {Gerald I.} and Yuhui Wang and Duncan, {Robin E.} and Chulho Kang and Sul, {Hei Sook}",

note = "Funding Information: This work was supported in part by DK75682 (H.S.S.), DK40936 (G.I.S.), and U24 DK076169 (V.T.S. and G.I.S.) from the National Institutes of Health. The authors thank R. Wong, A. Thompson, G. Wong, T. Liu, R. Mantara, T. Voortman, and E. Morse for technical and graphical assistance; A. Stahl and M. Kazantzis for help in metabolic chamber experiments; and A. Bradley for providing the pFlexible plasmid. ",

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doi = "10.1016/j.cmet.2011.05.002",

language = "English",

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T1 - Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype

AU - Ahmadian, Maryam

AU - Abbott, Marcia J.

AU - Tang, Tianyi

AU - Hudak, Carolyn S.S.

AU - Kim, Yangha

AU - Bruss, Matthew

AU - Hellerstein, Marc K.

AU - Lee, Hui Young

AU - Samuel, Varman T.

AU - Shulman, Gerald I.

AU - Wang, Yuhui

AU - Duncan, Robin E.

AU - Kang, Chulho

AU - Sul, Hei Sook

N1 - Funding Information: This work was supported in part by DK75682 (H.S.S.), DK40936 (G.I.S.), and U24 DK076169 (V.T.S. and G.I.S.) from the National Institutes of Health. The authors thank R. Wong, A. Thompson, G. Wong, T. Liu, R. Mantara, T. Voortman, and E. Morse for technical and graphical assistance; A. Stahl and M. Kazantzis for help in metabolic chamber experiments; and A. Bradley for providing the pFlexible plasmid.

PY - 2011/6/8

Y1 - 2011/6/8

N2 - While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated by AMPK at S406, increasing TAG hydrolase activity, and provide evidence for increased lipolysis by AMPK phosphorylation of desnutrin in adipocytes and in vivo. Despite adiposity and impaired BAT function, desnutrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis.

AB - While fatty acids (FAs) released by white adipose tissue (WAT) provide energy for other organs, lipolysis is also critical in brown adipose tissue (BAT), generating FAs for oxidation and UCP-1 activation for thermogenesis. Here we show that adipose-specific ablation of desnutrin/ATGL in mice converts BAT to a WAT-like tissue. These mice exhibit severely impaired thermogenesis with increased expression of WAT-enriched genes but decreased BAT genes, including UCP-1 with lower PPARα binding to its promoter, revealing the requirement of desnutrin-catalyzed lipolysis for maintaining a BAT phenotype. We also show that desnutrin is phosphorylated by AMPK at S406, increasing TAG hydrolase activity, and provide evidence for increased lipolysis by AMPK phosphorylation of desnutrin in adipocytes and in vivo. Despite adiposity and impaired BAT function, desnutrin-ASKO mice have improved hepatic insulin sensitivity with lower DAG levels. Overall, desnutrin is phosphorylated/activated by AMPK to increase lipolysis and brings FA oxidation and UCP-1 induction for thermogenesis.

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AN - SCOPUS:79958047295

SN - 1550-4131

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EP - 748

JO - Cell Metabolism

JF - Cell Metabolism

IS - 6

ER -

Desnutrin/ATGL is regulated by AMPK and is required for a brown adipose phenotype

Abstract

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