Regulation of Mitochondrial Metabolism in Murine Skeletal Muscle by the Medium-chain Fatty Acid Receptor Gpr84

Overview

Journal FASEB J

Specialties Biology
Physiology

Date 2019 Aug 16

PMID 31415180

Citations 25

Authors

Magdalene K Montgomery

Brenna Osborne

Amanda E Brandon

Liam OReilly

Corrine E Fiveash

Simon H J 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

Affiliations

Soon will be listed here.

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 [ 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.

Citing Articles

Medium-chain fatty acid receptor GPR84 deficiency leads to metabolic homeostasis dysfunction in mice fed high-fat diet.

Nishida A, Ohue-Kitano R, Masujima Y, Nonaka H, Igarashi M, Ikeda T FASEB Bioadv. 2024; 6(11):526-538.

PMID: 39512839 PMC: 11539033. DOI: 10.1096/fba.2024-00075.

Differential Effects of Three Medium-Chain Fatty Acids on Mitochondrial Quality Control and Skeletal Muscle Maturation.

Nishida R, Nukaga S, Kawahara I, Miyagawa Y, Goto K, Nakashima C Antioxidants (Basel). 2024; 13(7).

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PMID: 38814782 PMC: 11247419. DOI: 10.1016/j.celrep.2024.114288.

Targeting metabolic sensing switch GPR84 on macrophages for cancer immunotherapy.

Li J, Ma A, Zhang R, Chen Y, Bolyard C, Zhao B Cancer Immunol Immunother. 2024; 73(3):52.

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Immp2l Enhances the Structure and Function of Mitochondrial Gpd2 Dehydrogenase.

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