School of Life Science, Anhui Medical University, Hefei 230032, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Ganjiang Chinese Medicine Innovation Center, Nanchang 330000, China.
Int J Biol Macromol. 2023 Dec 31;253(Pt 1):126553. doi: 10.1016/j.ijbiomac.2023.126553. Epub 2023 Aug 30.
Several investigations have examined the involvement of free fatty acid receptor 4 (FFAR4) in metabolic disorders, but its action remains controversial. To investigate whether endogenous fibroblast growth factor 21 (FGF21)-mediated signaling controls the metabolic status in FFAR4-deficient mice, we generated FFAR4/FGF21 double knockout (DKO) mice. We also evaluated the role of FGF21 on glucose and lipid metabolism in FFAR4 KO mice fed a high-fat diet. Levels of FGF21 were significantly increased in FFAR4-deficient mice and double deletion of FGF21 and FFAR4 led to severe metabolic disorders. Additionally, FFAR4/FGF21 DKO mice displayed metabolic abnormalities that may be caused by decreased energy expenditure. Collectively, this study characterized the effects of endogenous FGF21, which acts as a master feedback regulator in the absence of FFAR4.
已有多项研究探讨了游离脂肪酸受体 4（FFAR4）在代谢紊乱中的作用，但它的作用仍存在争议。为了研究内源性成纤维细胞生长因子 21（FGF21）介导的信号是否控制 FFAR4 缺陷型小鼠的代谢状态，我们生成了 FFAR4/FGF21 双重敲除（DKO）小鼠。我们还评估了 FGF21 在高脂饮食喂养的 FFAR4 KO 小鼠中对葡萄糖和脂质代谢的作用。FFAR4 缺陷型小鼠的 FGF21 水平显著升高，而 FGF21 和 FFAR4 的双重缺失导致严重的代谢紊乱。此外，FFAR4/FGF21 DKO 小鼠表现出代谢异常，这可能是由于能量消耗减少所致。总的来说，这项研究描述了内源性 FGF21 的作用，它在没有 FFAR4 的情况下充当主反馈调节剂。
