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Regulation of mitochondrial metabolism in murine skeletal muscle by the medium‐chain fatty acid receptor Gpr84
Author(s) -
Montgomery Magdalene K.,
Osborne Brenna,
Brandon Amanda E.,
O'Reilly Liam,
Fiveash Corrine E.,
Brown Simon H. J.,
Wilkins Brendan P.,
Samsudeen Azrah,
Yu Josephine,
Devanapalli Beena,
Hertzog Ashley,
Tolun Adviye A.,
Kavanagh Tomas,
Cooper Antony A.,
Mitchell Todd W.,
Biden Trevor J.,
Smith Nicola J.,
Cooney Gregory J.,
Turner Nigel
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201900234r
Subject(s) - skeletal muscle , endocrinology , mitochondrial biogenesis , medicine , mitochondrion , receptor , fatty acid , adipose tissue , biology , metabolism , respiratory chain , fatty acid metabolism , beta oxidation , chemistry , microbiology and biotechnology , biochemistry
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. FASEB J. 33, 12264‐12276 (2019). www.fasebj.org