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Regulation of mitochondrial metabolism in murine skeletal muscle by the medium-chain fatty acid receptor Gpr84

Abstract

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 respiratory capacity of their skeletal muscle mitochondria, but at the same time also exhibit a substantial increase in mitochondrial content. Changes in canonical pathways of mitochondrial biogenesis and turnover are unable to explain these mitochondrial differences. Our results show that Gpr84 plays a crucial role in regulating mitochondrial function and quality control.-Montgomery, M. K., Osborne, B., Brandon, A. E., O'Reilly, L., Fiveash, C. E., Brown, S. H. J., Wilkins, B. P., Samsudeen, A., Yu, J., Devanapalli, B., Hertzog, A., Tolun, A. A., Kavanagh, T., Cooper, A. A., Mitchell, T. W., Biden, T. J., Smith, N. J., Cooney, G. J., Turner, N. Regulation of mitochondrial metabolism in murine skeletal muscle by the medium-chain fatty acid receptor Gpr84.

Type Journal
ISBN 1530-6860 (Electronic) 0892-6638 (Linking)
Authors Montgomery, M. K.; Osborne, B.; Brandon, A. E.; O'Reilly, L.; Fiveash, C. E.; Brown, S. H. J.; Wilkins, B. P.; Samsudeen, A.; Yu, J.; Devanapalli, B.; Hertzog, A.; Tolun, A. A.; Kavanagh, T.; Cooper, A. A.; Mitchell, T. W.; Biden, T. J.; Smith, N. J.; Cooney, G. J.; Turner, N.
Responsible Garvan Author Prof Trevor Biden
Publisher Name FASEB JOURNAL
Published Date 2019-11-01
Published Volume 33
Published Issue 11
Published Pages 12264-12276
Status Published in-print
DOI 10.1096/fj.201900234R
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/31415180