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The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.ORCID iD: 0000-0002-2915-6450
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Number of Authors: 182018 (English)In: EMBO Molecular Medicine, ISSN 1757-4676, E-ISSN 1757-4684, Vol. 10, no 3, article id e8047Article in journal (Refereed) Published
Abstract [en]

Brown adipose tissue (BAT) activation stimulates energy expenditure in human adults, which makes it an attractive target to combat obesity and related disorders. Recent studies demonstrated a role for G protein-coupled receptor 120 (GPR120) in BAT thermogenesis. Here, we investigated the therapeutic potential of GPR120 agonism and addressed GPR120-mediated signaling in BAT. We found that activation of GPR120 by the selective agonist TUG-891 acutely increases fat oxidation and reduces body weight and fat mass in C57Bl/6J mice. These effects coincided with decreased brown adipocyte lipid content and increased nutrient uptake by BAT, confirming increased BAT activity. Consistent with these observations, GPR120 deficiency reduced expression of genes involved in nutrient handling in BAT. Stimulation of brown adipocytes invitro with TUG-891 acutely induced O-2 consumption, through GPR120-dependent and GPR120-independent mechanisms. TUG-891 not only stimulated GPR120 signaling resulting in intracellular calcium release, mitochondrial depolarization, and mitochondrial fission, but also activated UCP1. Collectively, these data suggest that activation of brown adipocytes with the GPR120 agonist TUG-891 is a promising strategy to increase lipid combustion and reduce obesity.

Place, publisher, year, edition, pages
2018. Vol. 10, no 3, article id e8047
Keywords [en]
brown adipose tissue, Ca2+, GPR120, lipid metabolism, mitochondria
National Category
Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-154807DOI: 10.15252/emmm.201708047ISI: 000426769000003PubMedID: 29343498OAI: oai:DiVA.org:su-154807DiVA, id: diva2:1197669
Available from: 2018-04-13 Created: 2018-04-13 Last updated: 2018-04-13Bibliographically approved

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