Berberine Relieves Metabolic Syndrome in Mice by Inhibiting Liver Inflammation Caused by a High-Fat Diet and Potential Association With Gut Microbiota.

Jinjin Li,Guoying Wu,Hongzhao Sun,Caibo Zhang,Jianlei Jia,Shuzhen Wang,Jialin Li,Jiajia Ni

doi:10.3389/fmicb.2021.752512

Abstract

Whether berberine mediates its anti-inflammatory and blood sugar and lipid-lowering effects solely by adjusting the structure of the gut microbiota or by first directly regulating the expression of host pro-inflammatory proteins and activation of macrophages and subsequently acting on gut microbiota, is currently unclear. To clarify the mechanism of berberine-mediated regulation of metabolism, we constructed an obese mouse model using SPF-grade C57BL/6J male mice and conducted a systematic study of liver tissue pathology, inflammatory factor expression, and gut microbiota structure. We screened the gut microbiota targets of berberine and showed that the molecular mechanism of berberine-mediated treatment of metabolic syndrome involves the regulation of gut microbiota structure and the expression of inflammatory factors. Our results revealed that a high-fat diet (HFD) significantly changed mice gut microbiota, thereby probably increasing the level of toxins in the intestine, and triggered the host inflammatory response. The HFD also reduced the proportion of short-chain fatty acid (SCFA)-producing genes, thereby hindering mucosal immunity and cell nutrition, and increased the host inflammatory response and liver fat metabolism disorders. Further, berberine could improve the chronic HFD-induced inflammatory metabolic syndrome to some extent and effectively improved the metabolism of high-fat foods in mice, which correlated with the gut microbiota composition. Taken together, our study may improve our understanding of host-microbe interactions during the treatment of metabolic diseases and provide useful insights into the action mechanism of berberine.

Highlights

With a growing increase in changes in diet, lifestyle and other factors, there has been an explosive epidemic trend of metabolic syndrome characterized by obesity, type II diabetes, non-alcoholic fatty liver disease (NAFLD), and atherosclerosis (Ley et al, 2006; Turnbaugh et al, 2006; Zhang H. et al, 2010)
Thereafter, animals were divided into six groups (n = 10 per group) as follows: Normal chow diet (NCD group; 10% kcal from fat, Open Source Diets, D12450B), NCD supplemented with berberine [100 μg/kg/d body weight was suspended in 0.5% sodium carboxymethyl cellulose (CMC-Na) solution and fed through gavage; NCDBBR group], high-fat diet (HFD group; 60% kcal from fat, Open Source Diets, D12492), HFD supplemented with berberine (100 μg/kg/d body weight was suspended in 0.5% CMC-Na solution and fed through gavage; HFDBBR group), HFD supplemented with antibiotics (HFDABT group), and HFD supplemented with berberine and antibiotics (HFDBBRABT group)
The transcription levels of inducible nitric oxide synthase (iNOS) are usually significantly upregulated during liver inflammation (Menon and Sudheer, 2007), our results showed that HFD and berberine intervention significantly reduced iNOS expression levels

Summary

Introduction

With a growing increase in changes in diet, lifestyle and other factors, there has been an explosive epidemic trend of metabolic syndrome characterized by obesity, type II diabetes, non-alcoholic fatty liver disease (NAFLD), and atherosclerosis (Ley et al, 2006; Turnbaugh et al, 2006; Zhang H. et al, 2010). Various drugs are available to treat metabolic syndrome and its complications in the clinical setting, there is presently no specific treatment for this condition (Zhang et al, 2012, 2015; Chang et al, 2015). Metformin and acarbose can reduce blood sugar, its gastrointestinal side effects make it impossible for many patients to tolerate the maximum dose. Exploring the methods and mechanisms for prevention and treatment of metabolic syndrome has important theoretical and clinical application value

Methods

Results

Conclusion