Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3

Shannon M. Reilly; Chao Wei Hung; Maryam Ahmadian; Peng Zhao; Omer Keinan; Andrew V. Gomez; Julia H. DeLuca; Benyamin Dadpey; Donald Lu; Jessica Zaid; Bre Anne Poirier; Xiaoling Peng; Ruth T. Yu; Michael Downes; Christopher Liddle; Ronald M. Evans; Anne N. Murphy; Alan R. Saltiel

doi:10.1038/s42255-020-0217-6

Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3

Shannon M. Reilly, Chao Wei Hung, Maryam Ahmadian, Peng Zhao, Omer Keinan, Andrew V. Gomez, Julia H. DeLuca, Benyamin Dadpey, Donald Lu, Jessica Zaid, Bre Anne Poirier, Xiaoling Peng, Ruth T. Yu, Michael Downes, Christopher Liddle, Ronald M. Evans, Anne N. Murphy, Alan R. Saltiel

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

30 Scopus citations

Abstract

Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here, we report that catecholamines redirect FAs for oxidation through the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Adipocyte STAT3 is phosphorylated upon activation of β-adrenergic receptors, and in turn suppresses FA re-esterification to promote FA oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but exhibit defective lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity when they are on a high-fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and FA oxidation in adipocytes, revealing a new regulatory axis in metabolism.

Original language	English (US)
Pages (from-to)	620-634
Number of pages	15
Journal	Nature Metabolism
Volume	2
Issue number	7
DOIs	https://doi.org/10.1038/s42255-020-0217-6
State	Published - Jul 1 2020
Externally published	Yes

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism
Physiology (medical)
Cell Biology

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Reilly, S. M., Hung, C. W., Ahmadian, M., Zhao, P., Keinan, O., Gomez, A. V., DeLuca, J. H., Dadpey, B., Lu, D., Zaid, J., Poirier, B. A., Peng, X., Yu, R. T., Downes, M., Liddle, C., Evans, R. M., Murphy, A. N., & Saltiel, A. R. (2020). Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3. Nature Metabolism, 2(7), 620-634. https://doi.org/10.1038/s42255-020-0217-6

Reilly, SM, Hung, CW, Ahmadian, M, Zhao, P, Keinan, O, Gomez, AV, DeLuca, JH, Dadpey, B, Lu, D, Zaid, J, Poirier, BA, Peng, X, Yu, RT, Downes, M, Liddle, C, Evans, RM, Murphy, AN & Saltiel, AR 2020, 'Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3', Nature Metabolism, vol. 2, no. 7, pp. 620-634. https://doi.org/10.1038/s42255-020-0217-6

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abstract = "Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here, we report that catecholamines redirect FAs for oxidation through the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Adipocyte STAT3 is phosphorylated upon activation of β-adrenergic receptors, and in turn suppresses FA re-esterification to promote FA oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but exhibit defective lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity when they are on a high-fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and FA oxidation in adipocytes, revealing a new regulatory axis in metabolism.",

author = "Reilly, {Shannon M.} and Hung, {Chao Wei} and Maryam Ahmadian and Peng Zhao and Omer Keinan and Gomez, {Andrew V.} and DeLuca, {Julia H.} and Benyamin Dadpey and Donald Lu and Jessica Zaid and Poirier, {Bre Anne} and Xiaoling Peng and Yu, {Ruth T.} and Michael Downes and Christopher Liddle and Evans, {Ronald M.} and Murphy, {Anne N.} and Saltiel, {Alan R.}",

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AU - Keinan, Omer

AU - Gomez, Andrew V.

AU - DeLuca, Julia H.

AU - Dadpey, Benyamin

AU - Lu, Donald

AU - Zaid, Jessica

AU - Poirier, Bre Anne

AU - Peng, Xiaoling

AU - Yu, Ruth T.

AU - Downes, Michael

AU - Liddle, Christopher

AU - Evans, Ronald M.

AU - Murphy, Anne N.

AU - Saltiel, Alan R.

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N2 - Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here, we report that catecholamines redirect FAs for oxidation through the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Adipocyte STAT3 is phosphorylated upon activation of β-adrenergic receptors, and in turn suppresses FA re-esterification to promote FA oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but exhibit defective lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity when they are on a high-fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and FA oxidation in adipocytes, revealing a new regulatory axis in metabolism.

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Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3

Abstract

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