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A dysregulated bileacid-gut microbiotaaxis contributes toobesitysusceptibility Meilin WeiFengjie HuangLing Zhao2020 год

A dysregulated bile acid-gut microbiota axis contributes to obesity susceptibility
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Аннотация: BackgroundThe composition of the bile acid (BA) pool is closely associated with obesity and is modified by gut microbiota. Perturbations of gut microbiota shape the BA composition, which, in turn, may alter important BA signaling and affect host metabolism.MethodsWe investigated BA composition of high BMI subjects from a human cohort study and a high fat diet (HFD) obesity prone (HF-OP) / HFD obesity resistant (HF-OR) mice model. Gut microbiota was analysed by metagenomics sequencing. GLP-1 secretion and gene regulation studies involved ELISA, qPCR, Western blot, Immunohistochemistry, and Immunofluorescence staining.FindingsWe found that the proportion of non-12-OH BAs was significantly decreased in the unhealthy high BMI subjects. The HF-OR mice had an enhanced level of non-12-OH BAs. Non-12-OH BAs including ursodeoxycholate (UDCA), chenodeoxycholate (CDCA), and lithocholate (LCA) were decreased in the HF-OP mice and associated with altered gut microbiota. Clostridium scindens was decreased in HF-OP mice and had a positive correlation with UDCA and LCA. Gavage of Clostridium scindens in mice increased the levels of hepatic non-12-OH BAs, accompanied by elevated serum 7α-hydroxy-4-cholesten-3-one (C4) levels. In HF-OP mice, altered BA composition was associated with significantly downregulated expression of GLP-1 in ileum and PGC1α, UCP1 in brown adipose tissue. In addition, we identified that UDCA attenuated the high fat diet-induced obesity via enhancing levels of non-12-OH BAs.InterpretationOur study highlights that dysregulated BA signaling mediated by gut microbiota contributes to obesity susceptibility, suggesting modulation of BAs could be a promising strategy for obesity therapy.
Год издания: 2020
Авторы: Meilin Wei, Fengjie Huang, Ling Zhao, Yunjing Zhang, Wei Yang, Shouli Wang, Mengci Li, Xiaolong Han, Kun Ge, Chun Qu, Cynthia Rajani, Guoxiang Xie, Xiaojiao Zheng, Aihua Zhao, Zhaoxiang Bian, Jia Wang
Издательство: Elsevier BV
Источник: EBioMedicine
Ключевые слова: Drug Transport and Resistance Mechanisms, Gut microbiota and health, Diet and metabolism studies
Другие ссылки: EBioMedicine (PDF)
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DOAJ (DOAJ: Directory of Open Access Journals) (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)