Cited by 199Berberine and alkaloids researchDrug Transport and Resistance MechanismsGut microbiota and health

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Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway

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Sun, Runbin, Yang, Na, Kong, Bo, Cao, Bei, Feng, Dong, Yu, Xiaoyi, Ge, Chun, Huang, Jingqiu, Shen, Jianliang, Wang, Pei, Feng, Siqi, Fei, Fei, Guo, Jiahua, He, Jun, Aa, Nan, Chen, Qiang, Pan, Yang, Schumacher, Justin D., Yang, Chung S., Guo, Grace L., Aa, Jiye, Wang, Guangji·2017·Molecular Pharmacology

DOI 10.1124/mol.116.106617PMC PMC5267522

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Abstract

Previous studies suggest that the lipid-lowering effect of berberine (BBR) involves actions on the low-density lipoprotein receptor and the AMP-activated protein kinase signaling pathways. However, the implication of these mechanisms is unclear because of the low bioavailability of BBR. Because the main action site of BBR is the gut and intestinal farnesoid X receptor (FXR) plays a pivotal role in the regulation of lipid metabolism, we hypothesized that the effects of BBR on intestinal FXR signaling pathway might account for its pharmacological effectiveness. Using wild type (WT) and intestine-specific FXR knockout (FXR int-/-) mice, we found that BBR prevented the development of high-fat-diet-induced obesity and ameliorated triglyceride accumulation in livers of WT, but not FXR int-/- mice. BBR increased conjugated bile acids in serum and their excretion in feces. Furthermore, BBR inhibited bile salt hydrolase (BSH) activity in gut microbiota, and significantly increased the levels of tauro-conjugated bile acids, especially tauro-cholic acid(TCA), in the intestine. Both BBR and TCA treatment activated the intestinal FXR pathway and reduced the expression of fatty-acid translocase Cd36 in the liver. These results indicate that BBR may exert its lipid-lowering effect primarily in the gut by modulating the turnover of bile acids and subsequently the ileal FXR signaling pathway. In summary, we provide the first evidence to suggest a new mechanism of BBR action in the intestine that involves, sequentially, inhibiting BSH, elevating TCA, and activating FXR, which lead to the suppression of hepatic expression of Cd36 that results in reduced uptake of long-chain fatty acids in the liver.

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Authors: Sun, R., Yang, N., Kong, B., Cao, B., Feng, D., Yu, X., Ge, C., Huang, J., Shen, J., Wang, P., Feng, S., Fei, F., Guo, J., He, J., Aa, N., Chen, Q., Pan, Y., Schumacher, J. D., Yang, C. S., Guo, G. L., Aa, J., & Wang, G.
Affiliations: Rutgers, The State University of New Jersey (US)
ORCID: Sun, Runbin
Yang, Na
Kong, Bo
Feng, Dong
Yu, Xiaoyi
Ge, Chun
Feng, Siqi
Guo, Jiahua
He, Jun
Chen, Qiang
Pan, Yang
Schumacher, Justin D.
Yang, Chung S.
Guo, Grace L.
Aa, Jiye
Wang, Guangji
Venue: Molecular Pharmacology
Publisher: Elsevier BV
Published: 2017-02
Volume: 91
Issue: 2
Pages: 110-122
ISSN: 0026-895X (ISSN-L)
DOI: 10.1124/mol.116.106617
PMC: PMC5267522
OpenAlex: W2559834790
Cited by: 199
References: 68
Citations by year: 2026: 18 · 2025: 19 · 2024: 22 · 2023: 21 · 2022: 32 · 2021: 37 · 2020: 22 · 2019: 15 · 2018: 9 · 2017: 3
FWCI: 7.28
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Molecular Pharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of General Medical Sciences (R01GM104037)
National Institute of Environmental Health Sciences (T32ES007148)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Berberine and alkaloids research
Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords: berberine, hepatic lipid metabolism, bile acid metabolism, bile salt hydrolase, gut microbiota, taurocholate, CD36, fatty acid uptake, high-fat diet-induced obesity, triglyceride accumulation, hypolipidemic effect
MeSH terms: Gastrointestinal Microbiome, Receptor, Farnesoid X-Activated, Animals, Hypolipidemic Agents, Bacteria, Berberine, Bile Acids and Salts, Body Weight, Feces, Gene Expression Regulation, Intestinal Mucosa, Lithocholic Acid, Liver, Male, Mice, Inbred C57BL, Obesity, Taurocholic Acid, Triglycerides, Signal Transduction, Receptors, Cytoplasmic and Nuclear, CD36 Antigens, Lipid Metabolism, Diet, High-Fat

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Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway

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