The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat

Schilperoort, M, Dam, AD, Hoeke, G, Shabalina, IG, Okolo, A, Hanyaloglu, AC, Dib, LH, Mol, IM, Caengprasath, N, Chan, Y‐W, Damak, S, Miller, AR, Coskun, T, Shimpukade, B, Ulven, T, Kooijman, S, Rensen, PCN and Christian, M ORCID logoORCID: https://orcid.org/0000-0002-1616-4179, 2018. The GPR120 agonist TUG‐891 promotes metabolic health by stimulating mitochondrial respiration in brown fat. EMBO Molecular Medicine, 10 (3): e8047. ISSN 1757-4676

[thumbnail of 14378_Christian.pdf]
Preview
Text
14378_Christian.pdf - Published version

Download (3MB) | Preview

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 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.

Item Type: Journal article
Publication Title: EMBO Molecular Medicine
Creators: Schilperoort, M., Dam, A.D., Hoeke, G., Shabalina, I.G., Okolo, A., Hanyaloglu, A.C., Dib, L.H., Mol, I.M., Caengprasath, N., Chan, Y.W., Damak, S., Miller, A.R., Coskun, T., Shimpukade, B., Ulven, T., Kooijman, S., Rensen, P.C.N. and Christian, M.
Publisher: Wiley-Blackwell
Date: 2018
Volume: 10
Number: 3
ISSN: 1757-4676
Identifiers:
Number
Type
10.15252/emmm.201708047
DOI
Divisions: Schools > School of Science and Technology
Record created by: Jonathan Gallacher
Date Added: 12 Aug 2019 09:24
Last Modified: 12 Aug 2019 09:24
URI: https://irep.ntu.ac.uk/id/eprint/37220

Actions (login required)

Edit View Edit View

Statistics

Views

Views per month over past year

Downloads

Downloads per month over past year