Akebia saponin D ameliorates metabolic syndrome (MetS) via remodeling gut microbiota and attenuating intestinal barrier injury

作者：Song Yang, Ting Hu, He Liu, Yali Lv, Wen Zhang, Li Han, Lingling Xuan, Lili Gong, Lihong Liu · 发表于：Biomedicine & Pharmacotherapy · 年份：2021 · DOI：10.1016/j.biopha.2021.111441 · 被引用次数：49 · 研究领域：Gut microbiota and health、Ginseng Biological Effects and Applications、Clostridium difficile and Clostridium perfringens research

Metabolic syndrome (MetS) is a complex, multifactorial disease which lead to an increased risk of cardiovascular disease, type 2 diabetes, and stroke. However, selective, and potent drugs for the treatment of MetS are still lacking. Previous studies have found that Akebia saponin D (ASD) has beneficial effects on metabolic diseases such as obesity, atherosclerosis, and non-alcoholic fatty liver disease (NAFLD). Therefore, our study was designed to determine the effect and mechanism of action of ASD against MetS in a high-fat diet (HFD) induced mouse model. ASD significantly decreased plasma lipid and insulin resistance in these mice, and a targeted approach using metabolomic analyses of plasma and feces indicated that glucose and lipids in these mice crossed the damaged intestinal barrier into circulation. Furthermore, ASD was able to increase lipid excretion and inhibit intestinal epithelial lipid absorption. Results for gut microbiota composition showed that ASD significantly reduced HFD-associated Alistipes, Prevotella, and enhanced the proportions of Butyricimonas, Ruminococcus, and Bifidobacterium. After 14 weeks of ASD/fecal microbiota transplantation (FMT) interventions the developed gut barrier dysfunction was restored. Additionally, RNA-seq revealed that ASD reduced the lipid-induced tight junction (TJ) damage in intestinal epithelial cells via down-regulation of the PPAR-γ-FABP4 pathway in vitro and that use of the PPAR-γ inhibitor (T0070907) was able to partially b...