Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Obstetrics and Gynecology, Cheng Hsin General Hospital, Taipei, Taiwan.
Biochem Biophys Res Commun. 2020 Aug 27;529(3):714-719. doi: 10.1016/j.bbrc.2020.06.070. Epub 2020 Jul 18.
Obesity is associated with metabolic disorders. Fibroblast growth factor 21 (FGF21) has been recognized as important in metabolism. Glucosamine (GLN) has been demonstrated to perform diverse beneficial functions. This study aimed to reveal whether and how GLN would modulate FGF21 production in relation to metabolism. With in vivo model of normal diet (ND) and high-fat diet (HFD) mice receiving GLN injection and in vitro model of mouse AML12 liver cells and differentiated 3T3L1 adipocytes challenged with GLN, GLN appeared to improve the glucose metabolism in HFD and ND mice and to elevate FGF21 protein expression in HFD liver and to increase both FGF21 protein and mRNA levels in WAT from HFD and ND mice and it also upregulated FGF21 expression in both AML12 and differentiated 3T3L1 cells. By using inhibitors against various signaling pathways, p38, Akt, NF-κB, and PKA appeared potentially involved in GLN-mediated FGF21 production in AML12 cells; GLN was able to mediate activation of NF-κB, p38 or PKA/CREB signaling. Our accumulated findings suggest that GLN may potentially improve the metabolic performance by inducing FGF21 production in liver and adipose tissues and such induction in liver cells may act in part due to GLN induction of the NF-κB, p38 and PKA pathways.
肥胖与代谢紊乱有关。成纤维细胞生长因子 21（FGF21）在代谢中具有重要作用。已证实氨基葡萄糖（GLN）具有多种有益功能。本研究旨在揭示 GLN 是否以及如何调节代谢相关的 FGF21 产生。通过正常饮食（ND）和高脂肪饮食（HFD）小鼠的体内模型接受 GLN 注射以及 GLN 刺激的小鼠 AML12 肝细胞和分化的 3T3L1 脂肪细胞的体外模型，GLN 似乎改善了 HFD 和 ND 小鼠的葡萄糖代谢，并在 HFD 肝脏中升高 FGF21 蛋白表达，并在 HFD 和 ND 小鼠的 WAT 中增加 FGF21 蛋白和 mRNA 水平，还上调了 AML12 和分化的 3T3L1 细胞中的 FGF21 表达。通过使用针对各种信号通路的抑制剂，p38、Akt、NF-κB 和 PKA 似乎参与了 GLN 在 AML12 细胞中介导的 FGF21 产生；GLN 能够介导 NF-κB、p38 或 PKA/CREB 信号的激活。我们的研究结果表明，GLN 可能通过诱导肝脏和脂肪组织中 FGF21 的产生来改善代谢性能，而肝细胞中的这种诱导可能部分归因于 GLN 诱导的 NF-κB、p38 和 PKA 途径。
