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Exp Clin Endocrinol Diabetes 2018; 126(08): 513-520
DOI: 10.1055/s-0043-125066
Article
© Georg Thieme Verlag KG Stuttgart · New York

Berberine Modulates Gut Microbiota and Reduces Insulin Resistance via the TLR4 Signaling Pathway

Dan Liu   *
1   Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
,
Yiyi Zhang   *
1   Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
,
Yunhui Liu
2   Department of Endocrinology, Liuzhou Worker’s Hospital, Liuzhou 545005, China
,
Liqiong Hou
3   Department of Rheumatology, the First Hospital of Lanzhou University, Lanzhou 730000, China
,
Sheyu Li
1   Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
,
Haoming Tian
1   Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
,
Tieyun Zhao
1   Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China
› Author Affiliations
Further Information

Publication History

received 26 September 2017
first decision 13 December 2017

accepted 18 December 2017

Publication Date:
24 January 2018 (online)

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Abstract

Berberine, a natural compound extracted from several Chinese herbs including Coptis chinensis, has been shown to have anti-obesity effects and prevents insulin resistance in high-fat diet (HFD)-fed obese rats by modulating the gut microbiota; however, the molecular mechanisms underlying these activities remain unknown. We investigated the effects of berberine on obesity and insulin resistance by examining the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4)/tumor necrosis factor (TNF)-α signaling pathway in livers of HFD-fed obese rats. Our results showed that 8-week berberine (200 mg/kg) treatment significantly reduced fasting blood glucose, triglyceride, low-density lipoprotein-cholesterol and insulin resistance in HFD-fed obese rats. However, berberine had no significant effects on body weight, visceral fat mass or the visceral fat to body weight ratio. Berberine also attenuated HFD-induced hepatic steatosis. A prolonged HFD altered the gut microbiota composition by reducing protective bacteria like Bifidobacterium and increasing gram negative bacteria like Escherichia coli, which resulted in increased LPS release into plasma. Berberine reversed these effects and inhibited LPS-induced TLR4/TNF-α activation, resulting in increased insulin receptor and insulin receptor substrate-1 expression in the liver. These findings suggested that berberine may reduce insulin resistance, at least in part by modulating the gut microbiota along with inhibiting LPS/TLR4/TNF-α signaling in the liver.

Key words

berberine - gut microbiota - lipopolysaccharide - insulin resistance - TLR4

* These authors contributed equally to this work.


 

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