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

Song Yang; Ting Hu; He Liu; Ya-Li Lv; Wen Zhang; Han Li; Lingling Xuan; Li-Li Gong; Li-Hong Liu

doi:10.1016/j.biopha.2021.111441

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

Biomed Pharmacother. 2021 Jun:138:111441. doi: 10.1016/j.biopha.2021.111441. Epub 2021 Feb 27.

Authors

Song Yang¹, Ting Hu¹, He Liu¹, Ya-Li Lv¹, Wen Zhang¹, Han Li¹, Lingling Xuan¹, Li-Li Gong², Li-Hong Liu³

Affiliations

¹ Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
² Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA, USA. Electronic address: gonglili@126.com.
³ Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China. Electronic address: liulihong@bjcyh.com.

PMID: 33652261
DOI: 10.1016/j.biopha.2021.111441

Abstract

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 block the effects of ASD, indicating that the PPAR-γ/FABP4 pathway is a critical mediator involved in the improvement of MetS. Our results demonstrated that ASD not only modifies the gut microbiome but also ameliorates the HFD-induced gut barrier disruption via down-regulation of the PPAR-γ-FABP4 pathway. These findings suggest a promising, and novel therapeutic strategy for gut protection against MetS.

Keywords: Akebia saponin D; Gut barrier; Gut microbiota; Metabolic syndrome; PPAR-γ-FABP4.

MeSH terms

Animals
Cell Line
Fecal Microbiota Transplantation / methods
Gastrointestinal Microbiome / drug effects*
Gastrointestinal Microbiome / physiology
Humans
Intestinal Mucosa / drug effects*
Intestinal Mucosa / metabolism
Intestinal Mucosa / pathology
Male
Metabolic Syndrome / drug therapy*
Metabolic Syndrome / metabolism
Metabolic Syndrome / pathology
Mice
Mice, Inbred C57BL
Saponins / pharmacology
Saponins / therapeutic use*

Substances

Saponins
akebia saponin D