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

Autor: Nishida A; Department of Molecular Endocrinology, Graduate School of Pharmaceutical Sciences Kyoto University Kyoto Japan., Ohue-Kitano R; Department of Biological & Environmental Chemistry Kindai University Iizuka Japan., Masujima Y; Laboratory of Molecular Neurobiology, Graduate School of Biostudies Kyoto University Kyoto Japan., Nonaka H; Department of Applied Biological Science, Graduate School of Agriculture Tokyo University of Agriculture and Technology Fuchu Tokyo Japan., Igarashi M; Department of Applied Biological Science, Graduate School of Agriculture Tokyo University of Agriculture and Technology Fuchu Tokyo Japan., Ikeda T; Department of Molecular Endocrinology, Graduate School of Pharmaceutical Sciences Kyoto University Kyoto Japan.; Laboratory of Molecular Neurobiology, Graduate School of Biostudies Kyoto University Kyoto Japan., Kimura I; Department of Molecular Endocrinology, Graduate School of Pharmaceutical Sciences Kyoto University Kyoto Japan.; Laboratory of Molecular Neurobiology, Graduate School of Biostudies Kyoto University Kyoto Japan.
Jazyk: angličtina
Zdroj: FASEB bioAdvances [FASEB Bioadv] 2024 Oct 17; Vol. 6 (11), pp. 526-538. Date of Electronic Publication: 2024 Oct 17 (Print Publication: 2024).
DOI: 10.1096/fba.2024-00075
Abstrakt: Overconsumption of food, especially dietary fat, leads to metabolic disorders such as obesity and type 2 diabetes. Long-chain fatty acids, such as palmitoleate are recognized as the risk factors for these disorders owing to their high-energy content and lipotoxicity. In contrast, medium-chain fatty acids (MCFAs) metabolic benefits; however, their underlying molecular mechanisms remain unclear. GPR84 is an MCFA receptor, particularly for C10:0. Although evidence from in vitro experiments and oral administration of C10:0 in mice suggests that GPR84 is related to the metabolic benefits of MCFAs via glucose metabolism, its precise roles in vivo remain unclear. Therefore, the present study investigated whether GPR84 affects glucose metabolism and metabolic function using Gpr84 -deficient mice. Although Gpr84 -deficient mice were lean and had increased endogenous MCFAs under high-fat diet feeding conditions, they exhibited hyperglycemia and hyperlipidemia along with lower plasma insulin and glucagon-like peptide-1 (GLP-1) levels compared with wild-type mice. Medium-chain triglyceride (C10:0) intake suppressed obesity, and improved plasma glucose and lipid levels, and increased plasma GLP-1 levels in wild-type mice; however, these effects were partially attenuated in Gpr84 -deficient mice. Our results indicate that long-term MCFA-mediated GPR84 activation improves the dysfunction of glucose and lipid homeostasis. Our findings may be instrumental for future studies on drug development with GPR84 as a potential target, thereby offering new avenues for the treatment of metabolic disorders like obesity and type 2 diabetes.
(©2024 The Authors FASEB BioAdvances published by The Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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