UMMS Affiliation

Program in Molecular Medicine; Graduate School of Biomedical Sciences

Publication Date

2020-05-05

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Cell Biology | Cellular and Molecular Physiology | Endocrinology | Genetics and Genomics | Hormones, Hormone Substitutes, and Hormone Antagonists | Molecular Biology

Abstract

Here, we show that beta adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), and both effects are blocked in mice lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsalphaKO) in adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, beta3-adrenergic agonist CL316243 readily upregulates thermogenic but not lipogenic genes in cultured adipocytes, indicating that additional regulators must operate on DNL in sWAT in vivo. We identify one such factor as thyroid hormone T3, which is elevated locally by adrenergic signaling. T3 administration to wild-type mice enhances both thermogenesis and DNL in sWAT. Mechanistically, T3 action on UCP1 expression in sWAT depends upon cAMP and is blocked in Adipo-GsalphaKO mice even as elevated DNL persists. Thus, T3 enhances sWAT thermogenesis by amplifying cAMP signaling, while its control of adipocyte DNL can be mediated independently of both cAMP and rapamycin-sensitive mTORC1.

Keywords

Adrb3, Gs-alpha, beige adipocytes, cAMP, de novo lipogenesis, mTORC1, sympathetic nerve, thyroid hormones

Rights and Permissions

Copyright 2020 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

DOI of Published Version

10.1016/j.celrep.2020.107598

Source

Guilherme A, Yenilmez B, Bedard AH, Henriques F, Liu D, Lee A, Goldstein L, Kelly M, Nicoloro SM, Chen M, Weinstein L, Collins S, Czech MP. Control of Adipocyte Thermogenesis and Lipogenesis through β3-Adrenergic and Thyroid Hormone Signal Integration. Cell Rep. 2020 May 5;31(5):107598. doi: 10.1016/j.celrep.2020.107598. PMID: 32375048. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

32375048

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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