Liu Shui-Yu, Chen Luen-Kui, Li Pin-Hsuan, Wu Guan-Lin, Wu Tsung-Hui, Yu Yuan-Bin, Lin Heng-Fu, Juan Chi-Chang
Institutes of Physiology, College of Medicine, National Yang Ming Chiao Tung University, No. 155, Sec. 2, Linong St., Beitou District, Taipei, 112304, Taiwan.
Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Rd., Beitou District, Taipei, 112201, Taiwan.
Sci Rep. 2025 Apr 16;15(1):13096. doi: 10.1038/s41598-025-96249-3.
Glucosamine (GlcN) is a common supplement used to alleviate osteoarthritis, but it may dysregulate glucose tolerance and induce insulin resistance, thereby increasing metabolic burden. The liver is a vital organ that modulates the Akt/mTOR/p70S6K signaling pathway in response to growth and metabolism. Fibroblast growth factor 21 (FGF21) is a hepatokine involved in regulating glucose and lipid metabolism. Additionally, increased circulating FGF21 levels have been linked to the prediction of metabolic disorders and type 2 diabetes. However, the regulatory mechanism controlling FGF21 expression by GlcN remains unclear. In the present study, GlcN stimulation led to several outcomes, including an increase in cell content, secretion, and mRNA and protein levels of FGF21 in hepatocytes. Moreover, inhibition of the Akt/mTOR/p70S6K axis resulted in reduced FGF21 expression in response to GlcN. Importantly, GlcN-mediated expression of FGF21 relies on PGC-1α upregulation. These results suggest that GlcN increases FGF21 expression through the activation between Akt/mTOR/p70S6K pathway and PGC-1α dependent manner.
氨基葡萄糖（GlcN）是一种常用于缓解骨关节炎的补充剂，但它可能会扰乱葡萄糖耐量并诱导胰岛素抵抗，从而增加代谢负担。肝脏是一个重要器官，可响应生长和代谢调节Akt/mTOR/p70S6K信号通路。成纤维细胞生长因子21（FGF21）是一种参与调节葡萄糖和脂质代谢的肝因子。此外，循环中FGF21水平升高与代谢紊乱和2型糖尿病的预测有关。然而，GlcN控制FGF21表达的调节机制仍不清楚。在本研究中，GlcN刺激导致了多种结果，包括肝细胞中FGF21的细胞含量、分泌以及mRNA和蛋白质水平增加。此外，抑制Akt/mTOR/p70S6K轴会导致对GlcN反应时FGF21表达降低。重要的是，GlcN介导的FGF21表达依赖于PGC-1α上调。这些结果表明，GlcN通过Akt/mTOR/p70S6K途径与PGC-1α依赖性方式之间的激活增加FGF21表达。
