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

FASEB J. 2019 Nov;33(11):12264-12276. doi:10.1096/fj.201900234R. Epub 2019 Aug 15
Magdalene K Montgomery 1 , Brenna Osborne 2 , Amanda E Brandon 3 , Liam O'Reilly 4 , Corrine E Fiveash 2 , Simon H J Brown 5 , Brendan P Wilkins 6 , Azrah Samsudeen 2 , Josephine Yu 2 , Beena Devanapalli 7 , Ashley Hertzog 7 , Adviye A Tolun 8 , Tomas Kavanagh 9 , Antony A Cooper 10 , Todd W Mitchell 11 , Trevor J Biden 10 , Nicola J Smith 10 , Gregory J Cooney 3 , Nigel Turner 2
Magdalene K Montgomery 1 , Brenna Osborne 2 , Amanda E Brandon 3 , Liam O'Reilly 4 , Corrine E Fiveash 2 , Simon H J Brown 5 , Brendan P Wilkins 6 , Azrah Samsudeen 2 , Josephine Yu 2 , Beena Devanapalli 7 , Ashley Hertzog 7 , Adviye A Tolun 8 , Tomas Kavanagh 9 , Antony A Cooper 10 , Todd W Mitchell 11 , Trevor J Biden 10 , Nicola J Smith 10 , Gregory J Cooney 3 , Nigel Turner 2
+ et al

[No authors listed]

Author information
  • 1 Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, Victoria, Australia.
  • 2 Department of Pharmacology, School of Medical Sciences, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia.
  • 3 Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia.
  • 4 Diabetes and Metabolism Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
  • 5 Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Australia.
  • 6 Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
  • 7 New South Wales (NSW) Biochemical Genetics Laboratory, Sydney Children's Hospital Network, Westmead, New South Wales, Australia.
  • 8 Discipline of Child and Adolescent Health, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
  • 9 Neuroscience Division, Garvan Institute of Medical Research, Sydney, New South Wales, Australia.
  • 10 St. Vincent's Clinical School, University of New South Wales (UNSW) Sydney, Sydney, New South Wales, Australia.
  • 11 School of Medicine, University of Wollongong, Wollongong, New South Wales, Australia.

摘要

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.

KEYWORDS: insulin resistance, insulin secretion, mitochondrial function

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