Chlorogenic Acid Improves NAFLD by Regulating gut Microbiota and GLP-1

Ameng Shi; Ting Li; Ying Zheng; Yahua Song; Haitao Wang; Na Wang; Lei Dong; Haitao Shi

doi:10.3389/fphar.2021.693048

Chlorogenic Acid Improves NAFLD by Regulating gut Microbiota and GLP-1

Front Pharmacol. 2021 Jun 30:12:693048. doi: 10.3389/fphar.2021.693048. eCollection 2021.

Authors

Ameng Shi¹, Ting Li², Ying Zheng³, Yahua Song³, Haitao Wang⁴, Na Wang⁴, Lei Dong³, Haitao Shi³

Affiliations

¹ Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Geriatric Respiratory and Endocrinology (The Third Unit of Cadre's Ward), The Second Affiliated Hospital of Xian Jiaotong University, Xi'an, China.
³ Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Department of Pharmacy, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Abstract

Our previous studies have shown that chlorogenic acid (CGA) could significantly improve acute and chronic liver injury through antioxidant and anti-inflammatory activities. However, its effect on non-alcoholic fatty liver disease (NAFLD) are not entirely clear. This study aims to explore the effect of CGA on NAFLD induced by high-fat diet (HFD) and whether it regulates the gut microbiota and Glucagon-like peptide-1 (GLP-1). NAFLD mice were established by HFD and treated with or without CGA. Serum transaminase, fasting blood glucose (FBG), blood lipids, insulin, GLP-1 and lipopolysaccharide (LPS) were detected. Liver histology was evaluated with Hematoxylin-eosin staining. Toll like receptor 4 (TLR4) signaling pathway was analyzed with western blot and inflammatory cytokines were detected with real-time PCR. The content of gut microbiota were determined with real-time PCR of the bacterial 16S rRNA gene. Expressions of intestine tight junctional protein were examined with immunohistochemistry. CGA could alleviate HFD-induced hepatic steatosis and inflammation, reduce serum transaminase, FBG and blood lipids, increase insulin sensitivity. CGA also could reverse HFD-induced activation of TLR4 signaling pathway and expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver. Meanwhile, CGA increased the content of Bifidobacterium and reduced the content of Escherichia coli in feces. Furthermore, CGA could increase the expression of tight junction proteins Occludin and zonula occludens-1 (ZO-1) in intestinal tissue. Moreover, CGA could the level of LPS and increased the level of GLP-1 in portal vein. These results indicated that CGA protected against HFD-induced hepatic steatosis and inflammation probably through its anti-inflammatory effects associated with regulation of gut microbiota and an increase of GLP-1 secretion and thus could be used as a potential drug for prevention and treatment of NAFLD.

Keywords: anti-inflammatory; chlorogenic acid; glucagon-like peptide-1; gut microbiota; non-alcoholic fatty liver disease.