中链脂肪酸受体 GPR84 缺乏会导致高脂饮食小鼠代谢平衡失调

IF 2.5 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Akari Nishida, Ryuji Ohue-Kitano, Yuki Masujima, Hazuki Nonaka, Miki Igarashi, Takako Ikeda, Ikuo Kimura
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引用次数: 0

摘要

过度摄入食物,尤其是膳食脂肪,会导致肥胖和 2 型糖尿病等代谢紊乱。棕榈油酸等长链脂肪酸因其高能量和脂肪毒性被认为是导致这些疾病的风险因素。与此相反,中链脂肪酸(MCFAs)对新陈代谢有益,但其潜在的分子机制仍不清楚。GPR84 是一种 MCFA 受体,尤其是 C10:0 受体。虽然体外实验和小鼠口服 C10:0 的证据表明,GPR84 与 MCFAs 通过葡萄糖代谢带来的代谢益处有关,但其在体内的确切作用仍不清楚。因此,本研究利用 Gpr84 缺失的小鼠研究 GPR84 是否影响葡萄糖代谢和代谢功能。与野生型小鼠相比,Gpr84 缺失型小鼠虽然瘦小,而且在高脂饮食喂养条件下内源性 MCFAs 增加,但它们表现出高血糖和高脂血症,血浆胰岛素和胰高血糖素样肽-1(GLP-1)水平较低。摄入中链甘油三酯(C10:0)可抑制肥胖,改善血糖和血脂水平,并提高野生型小鼠的血浆 GLP-1 水平;但这些作用在 Gpr84 基因缺陷小鼠中部分减弱。我们的研究结果表明,MCFA 介导的 GPR84 长期激活可改善葡萄糖和脂质平衡失调。我们的发现可能有助于未来以 GPR84 为潜在靶点的药物开发研究,从而为治疗肥胖和 2 型糖尿病等代谢性疾病提供新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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

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

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.

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来源期刊
FASEB bioAdvances
FASEB bioAdvances Multiple-
CiteScore
5.40
自引率
3.70%
发文量
56
审稿时长
10 weeks
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