Control of Adipocyte Thermogenesis and Lipogenesis through beta3-Adrenergic and Thyroid Hormone Signal Integration
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Publisher version
Document Type
Journal ArticlePublication Date
2020-05-05Keywords
Adrb3Gs-alpha
beige adipocytes
cAMP
de novo lipogenesis
mTORC1
sympathetic nerve
thyroid hormones
Amino Acids, Peptides, and Proteins
Cell BiologyCellular and Molecular PhysiologyEndocrinologyGenetics and GenomicsHormones, Hormone Substitutes, and Hormone AntagonistsMolecular Biology
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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.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
DOI
10.1016/j.celrep.2020.107598Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41459PubMed ID
32375048Related Resources
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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/)Distribution License
http://creativecommons.org/licenses/by-nc-nd/4.0/Scopus Count
Except where otherwise noted, this item's license is described as 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/)
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