Open AccessThe GPR 120 agonist TUG ‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat
Author(s) -
Schilperoort Maaike,
Dam Andrea D,
Hoeke Geerte,
Shabalina Irina G,
Okolo Anthony,
Hanyaloglu Aylin C,
Dib Lea H,
Mol Isabel M,
Caengprasath Natarin,
Chan YiWah,
Damak Sami,
Miller Anne Reifel,
Coskun Tamer,
Shimpukade Bharat,
Ulven Trond,
Kooijman Sander,
Rensen Patrick CN,
Christian Mark
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708047
Subject(s) - medicine , library science , computer science
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 ( GPR 120) in BAT thermogenesis. Here, we investigated the therapeutic potential of GPR 120 agonism and addressed GPR 120‐mediated signaling in BAT . We found that activation of GPR 120 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, GPR 120 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 GPR 120‐dependent and GPR 120‐independent mechanisms. TUG ‐891 not only stimulated GPR 120 signaling resulting in intracellular calcium release, mitochondrial depolarization, and mitochondrial fission, but also activated UCP 1. Collectively, these data suggest that activation of brown adipocytes with the GPR 120 agonist TUG ‐891 is a promising strategy to increase lipid combustion and reduce obesity.