The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
Year: 2018
Type: article
Abstract: 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 in vitro with TUG-891 acutely induced O 2 consumption, through GPR120dependent 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.
Source: EMBO Molecular Medicine
Authors: Maaike Schilperoort, Andrea D van Dam, Geerte Hoeke, Irina G Shabalina, Anthony Okolo, Aylin C Hanyaloglu, Lea H Dib, Isabel M Mol, Natarin Caengprasath, Yi‐Wah Chan, Sami Damak, Anne Reifel Miller, Tamer Coskun, Bharat Shimpukade, Trond Ulven, Sander Kooijman, Patrick CN Rensen, Mark Christian
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,990
Funders: Eli Lilly and Company, Strategiske Forskningsråd, Genesis Research Trust, Research Councils UK, University of Warwick, European Commission, Universiteit Leiden, Hartstichting, Leids Universitair Medisch Centrum, Stockholms Universitet, Rembrandt Institute of Cardiovascular Science, Directorate for Biological Sciences, Biotechnology and Biological Sciences Research Council, Warwick Medical School
Awards: Recruitment and activation of brown adipocytes as preventive and curative therapy for type 2 diabetes, Role of CIDE proteins in lipid droplet formation and adipocyte metabolism, G2409481481, G289321774, G4045985073, G4716923584, G512630550, G6953968003, G7186044699, CIDEA-dependent lipid droplet induction in C. elegans, Evaluation of Rgs7 as a key regulator of adipocyte function, G8822115220, G901660965
OpenAlex ID: W2782830373