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| [PMID]: | 27932556 |
| [Au] Autor: | 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 JD; Yang CS; Guo GL; Aa J; Wang G |
| [Ad] Endereço: | State Key Laboratory of Natural Medicines, Jiangsu Province Key Laboratory of Drug Metabolism and Pharmacokinetics, Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, China (R.S., N.Y., D.F., X.Y., C.G., J.H., P.W., S.F., F.F. J.G., J.H., N.A., Q.C., J. |
| [Ti] Título: | Orally Administered Berberine Modulates Hepatic Lipid Metabolism by Altering Microbial Bile Acid Metabolism and the Intestinal FXR Signaling Pathway. |
| [So] Source: | Mol Pharmacol;91(2):110-122, 2017 Feb. | | [Is] ISSN: | 1521-0111 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | 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 ) 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 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. |
| [Mh] Termos MeSH primário: |
Bactérias/metabolismo
Berberina/administração & dosagem
Berberina/farmacologia
Ácidos e Sais Biliares/metabolismo
Intestinos/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Fígado/metabolismo
Receptores Citoplasmáticos e Nucleares/metabolismo
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| [Mh] Termos MeSH secundário: |
Animais
Bactérias/efeitos dos fármacos
Berberina/uso terapêutico
Ácidos e Sais Biliares/sangue
Peso Corporal/efeitos dos fármacos
Antígenos CD36/genética
Antígenos CD36/metabolismo
Dieta Hiperlipídica
Fezes/química
Microbioma Gastrointestinal/efeitos dos fármacos
Regulação da Expressão Gênica/efeitos dos fármacos
Hipolipemiantes/farmacologia
Hipolipemiantes/uso terapêutico
Metabolismo dos Lipídeos/genética
Ácido Litocólico/farmacologia
Fígado/efeitos dos fármacos
Masculino
Camundongos Endogâmicos C57BL
Obesidade/sangue
Obesidade/tratamento farmacológico
Obesidade/genética
Obesidade/prevenção & controle
Transdução de Sinais/efeitos dos fármacos
Ácido Taurocólico/farmacologia
Triglicerídeos/metabolismo
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| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (Bile Acids and Salts); 0 (CD36 Antigens); 0 (Hypolipidemic Agents); 0 (Receptors, Cytoplasmic and Nuclear); 0 (Triglycerides); 0 (farnesoid X-activated receptor); 0I8Y3P32UF (Berberine); 5E090O0G3Z (Taurocholic Acid); 5QU0I8393U (Lithocholic Acid) |
| [Em] Mês de entrada: | 1705 |
| [Cu] Atualização por classe: | 171116 |
[Lr] Data última revisão:
| 171116 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 161210 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1124/mol.116.106617 |
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