The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
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The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat. / Schilperoort, Maaike; van Dam, Andrea D; Hoeke, Geerte; Shabalina, Irina G; Okolo, Anthony; Hanyaloglu, Aylin C; Dib, Lea H; Mol, Isabel M; Caengprasath, Natarin; Chan, Yi-Wah; Damak, Sami; Miller, Anne Reifel; Coskun, Tamer; Shimpukade, Bharat; Ulven, Trond; Kooijman, Sander; Rensen, Patrick Cn; Christian, Mark.
In: E M B O Molecular Medicine, Vol. 10, No. 3, e8047, 17.01.2018.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - The GPR120 agonist TUG-891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
AU - Schilperoort, Maaike
AU - van Dam, Andrea D
AU - Hoeke, Geerte
AU - Shabalina, Irina G
AU - Okolo, Anthony
AU - Hanyaloglu, Aylin C
AU - Dib, Lea H
AU - Mol, Isabel M
AU - Caengprasath, Natarin
AU - Chan, Yi-Wah
AU - Damak, Sami
AU - Miller, Anne Reifel
AU - Coskun, Tamer
AU - Shimpukade, Bharat
AU - Ulven, Trond
AU - Kooijman, Sander
AU - Rensen, Patrick Cn
AU - Christian, Mark
N1 - © 2018 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2018/1/17
Y1 - 2018/1/17
N2 - 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 O2 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.
AB - 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 O2 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.
KW - Journal Article
U2 - 10.15252/emmm.201708047
DO - 10.15252/emmm.201708047
M3 - Journal article
C2 - 29343498
VL - 10
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 3
M1 - e8047
ER -
ID: 189159353