Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, CA, USA.
Department of Food Science and Technology, Department of Viticulture and Enology, University of California, Davis, CA, USA.
Sci Rep. 2017 May 11;7(1):1748. doi: 10.1038/s41598-017-01576-9.
This study aims to uncover how specific bacteria and bile acids (BAs) contribute to steatosis induced by diet and farnesoid X receptor (FXR) deficiency in both genders. A control diet (CD) and Western diet (WD), which contains high fat and carbohydrate, were used to feed wild type (WT) and FXR knockout (KO) mice followed by phenotyping characterization as well as BA and microbiota profiling. Our data revealed that male WD-fed FXR KO mice had the most severe steatosis and highest hepatic and serum lipids as well as insulin resistance among the eight studied groups. Gender differences in WD-induced steatosis, insulin sensitivity, and predicted microbiota functions were all FXR-dependent. FXR deficiency enriched Desulfovibrionaceae, Deferribacteraceae, and Helicobacteraceae, which were accompanied by increased hepatic taurine-conjugated cholic acid and β-muricholic acid as well as hepatic and serum lipids. Additionally, distinct microbiota profiles were found in WD-fed WT mice harboring simple steatosis and CD-fed FXR KO mice, in which the steatosis had a potential to develop into liver cancer. Together, the presented data revealed FXR-dependent concomitant relationships between gut microbiota, BAs, and metabolic diseases in both genders. Gender differences in BAs and microbiota may account for gender dissimilarity in metabolism and metabolic diseases.
本研究旨在揭示特定细菌和胆汁酸（BAs）如何导致饮食和法尼醇 X 受体（FXR）缺乏在两性中引起的脂肪变性。使用对照饮食（CD）和含有高脂肪和碳水化合物的西方饮食（WD）喂养野生型（WT）和 FXR 敲除（KO）小鼠，然后进行表型特征以及 BA 和微生物组分析。我们的数据表明，在研究的八个组中，雄性 WD 喂养的 FXR KO 小鼠的脂肪变性、肝和血清脂质以及胰岛素抵抗最为严重。WD 诱导的脂肪变性、胰岛素敏感性和预测的微生物组功能在性别上的差异均依赖于 FXR。FXR 缺乏使脱硫弧菌科、脱硫杆菌科和螺旋杆菌科富集，伴随着肝牛磺酸结合胆酸和β-鼠胆酸以及肝和血清脂质的增加。此外，在 WD 喂养的 WT 小鼠中发现了不同的微生物组谱，这些小鼠仅存在单纯性脂肪变性，而在 CD 喂养的 FXR KO 小鼠中，脂肪变性有可能发展为肝癌。总之，所呈现的数据揭示了 FXR 在两性中肠道微生物群、BAs 和代谢疾病之间的依赖关系。BAs 和微生物组在性别上的差异可能解释了代谢和代谢疾病在性别上的差异。
