我们先前的研究表明，苦荞根多糖（TBRP）能通过抑制SOCS3促进的IRS1蛋白降解来降低糖尿病的胰岛素抵抗性。然而，TBRP是否具有治疗非酒精性脂肪肝（NAFLD）的效应仍未确定。本研究旨在研究TBRP对高脂饮食（HFD）引发的NAFLD的影响，并阐明其潜在的分子机制。简单来说，通过体外和体内评估TBRP在肝癌细胞（BEL7404）、胰腺癌细胞（BxPC3）和斑马鱼胚胎发育模型中的毒性。TBRP通过抑制脂肪合成来抑制细胞脂质积累，此外，它改善了NAFLD小鼠模型中的体重增加、肝重、肝体重比、血清脂肪甘油三酯、总胆固醇、ALT、LDL-C、HDL-C和AST水平。此外，TBRP处理还降低了一氧化氮含量。qPCR分析显示，TBRP处理后NAFLD小鼠中的TNF、IL1β和IL6的mRNA表达也明显降低。通过Western blot分析显示，TBRP显著降低了SOCS3、SREBP1c和STAT3的基因表达，表明TBRP通过SOCS3-SREBP1c通路显著降低了脂肪新生的基因表达。这些发现揭示了TBRP通过IL6-SOCS3-SREBP1c信号通路改善NAFLD，因此可能是治疗NAFLD的一种有前景的方法。版权所有 © 2023 Elsevier Ltd.

Our previous study demonstrated that Tartary buckwheat root polysaccharides (TBRP) could reduce insulin resistance in diabetes mellitus by inhibiting SOCS3-stimulated IRS1 protein degradation. However, whether TBRP has the efficiency to treat non-alcoholic fatty liver disease (NAFLD) is still undetermined. This investigation aimed to examine the effects of TBRP on a high-fat diet (HFD)-triggered NAFLD, and elucidate the underlying molecular mechanisms. Briefly, TBRP toxicity in hepatoma (BEL7404) and pancreatic cancer (BxPC3) cells and zebrafish embryos developmental models, were evaluated in-vitro and in-vivo, respectively. TBRP inhibited cellular lipid accumulation by suppressing fat synthesis, furthermore, it improved body weight gain, liver weight, liver-to-body weight ratio, serum lipids triglyceride, total cholesterol, ALT, LDL-C, HDL-C, and AST levels in the NAFLD mice model. Additionally, TBRP treatment also lowered the nitric oxide content. The qPCR assay revealed that mRNA expression of TNF, IL1β, and IL6 was also markedly reduced in TBRP-treated NAFLD mice. The expression of SOCS3, SREBP1c, and STAT3 was elucidated by western blot analysis, which indicated that TBRP markedly decreased the gene expression for de novo fat synthesis by the SOCS3-SREBP1c pathway. These findings reveal that TBRP ameliorates NAFLD via the IL6-SOCS3-SREBP1c signaling pathway and therefore, may represent a promising approach for NAFLD treatment.Copyright © 2023. Published by Elsevier Ltd.