Regulation of mitochondrial metabolism in murine skeletal muscle by the medium-chain fatty acid receptor Gpr84
Magdalene K Montgomery, Brenna Osborne, Amanda E Brandon, Liam O'Reilly, Corrine E Fiveash, Simon HJ Brown, Brendan P Wilkins, Azrah Samsudeen, Josephine Yu, Beena Devanapalli, Ashley Hertzog, Adviye A Tolun, Tomas Kavanagh, Antony A Cooper, Todd W Mitchell, Trevor J Biden, Nicola J Smith, Gregory J Cooney, Nigel Turner
FASEB JOURNAL | WILEY | Published : 2019
Fatty acid receptors have been recognized as important players in glycaemic control. This study is the first to describe a role for the medium-chain fatty acid (MCFA) receptor G-protein-coupled receptor (Gpr) 84 in skeletal muscle mitochondrial function and insulin secretion. We are able to show that Gpr84 is highly expressed in skeletal muscle and adipose tissue. Mice with global deletion of Gpr84 [Gpr84 knockout (KO)] exhibit a mild impairment in glucose tolerance when fed a MCFA-enriched diet. Studies in mice and pancreatic islets suggest that glucose intolerance is accompanied by a defect in insulin secretion. MCFA-fed KO mice also exhibit a significant impairment in the intrinsic respir..View full abstract
Awarded by NIH National Human Genome Research Institute (NHGRI)
Awarded by CSD Consortium
Awarded by Children's Hospital Oakland Research Institute (CHORI)
The authors thank Prof. Bob Graham (Victor Chang Cardiac Research Institute) and Dr. Michael Lazarou (Monash University, Melbourne, VIC, Australia) for generous advice on aspects of this study. This work was supported by funding from the National Health and Medical Research Council of Australia, the Australian Research Council, and the University of Wollongong. M.K.M. was supported by a National Health and Medical Research Council (NHMRC) Career Development Fellowship. Gpr84tm1(KOMP)Vlcg embryonic stem cells used for this research project were generated by the Trans-U.S. National Institutes of Health (NIH) Knockout Mouse Project and obtained from the Knockout Mouse Project Repository (www.komp.org).NIH National Human Genome Research Institute (NHGRI) Grant U01HG004085 to Velocigene at Regeneron, and the CSD Consortium (U01HG004080) funded the generation of gene-targeted embryonic stem cells for 8500 genes in the Knockout Mouse Project Program and archived and distributed by the Knockout Mouse Project Repository at the University of California-Davis (Davis, CA, USA), and Children's Hospital Oakland Research Institute (CHORI; U42RR024244). Animal work was made possible thanks to kind staff in the University of New South Wales Biological Resources Centre and the Garvan Institute Biological Testing Facility. The authors declare no conflicts of interest.