GPR180 is a component of TGFβ signalling that promotes thermogenic adipocyte function and mediates the metabolic effects of the adipocyte-secreted factor CTHRC1.

Adipocytes, Beige / metabolism Adipocytes, Brown / metabolism Animals Energy Metabolism Extracellular Matrix Proteins / genetics Glucose Homeostasis Humans Male Metabolic Diseases / genetics Metabolic Syndrome / genetics Mice, Inbred C57BL Mice, Knockout Receptors, G-Protein-Coupled / genetics Signal Transduction / genetics Thermogenesis / genetics Transforming Growth Factor beta / metabolism

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
08 12 2021

Historique:

received: 10 06 2021

accepted: 17 11 2021

entrez: 9 12 2021

pubmed: 10 12 2021

medline: 11 1 2022

Statut: epublish

Résumé

Activation of thermogenic brown and beige adipocytes is considered as a strategy to improve metabolic control. Here, we identify GPR180 as a receptor regulating brown and beige adipocyte function and whole-body glucose homeostasis, whose expression in humans is associated with improved metabolic control. We demonstrate that GPR180 is not a GPCR but a component of the TGFβ signalling pathway and regulates the activity of the TGFβ receptor complex through SMAD3 phosphorylation. In addition, using genetic and pharmacological tools, we provide evidence that GPR180 is required to manifest Collagen triple helix repeat containing 1 (CTHRC1) action to regulate brown and beige adipocyte activity and glucose homeostasis. In this work, we show that CTHRC1/GPR180 signalling integrates into the TGFβ signalling as an alternative axis to fine-tune and achieve low-grade activation of the pathway to prevent pathophysiological response while contributing to control of glucose and energy metabolism.

Identifiants

DOI: 10.1038/s41467-021-27442-x PMID: 34880217 PMC: PMC8655035

pubmed: 34880217

doi: 10.1038/s41467-021-27442-x

pii: 10.1038/s41467-021-27442-x

pmc: PMC8655035

doi:

Substances chimiques

CTHRC1 protein, human 0

Extracellular Matrix Proteins 0

GPR180 protein, human 0

Receptors, G-Protein-Coupled 0

Transforming Growth Factor beta 0

Glucose IY9XDZ35W2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

7144

Informations de copyright

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