胆汁酸
生物
昼夜节律
肠道菌群
内分泌学
内科学
葡萄糖稳态
微生物群
新陈代谢
碳水化合物代谢
胰岛素
平衡
胰岛素抵抗
生物化学
医学
生物信息学
作者
Xiaozhen Guo,Jiawen Wang,Hongwei Xu,Yangyang Wang,Yi Cao,Yuan Wen,Jiaqi Li,Yameng Liu,Kanglong Wang,Jue Wang,Xianchun Zhong,Chuying Sun,Y.Y. Zhang,Jingyi Xu,Cuina Li,Panwei Mu,Lingyan Xu,Cen Xie
标识
DOI:10.1016/j.bbalip.2023.159419
摘要
The disruption of the diurnal rhythm has been recognized as a significant contributing factor to metabolic dysregulation. The important role of gut microbiota and bile acid metabolism has attracted extensive attention. However, the function of the gut microbiota-bile acid axis in regulating the diurnal rhythms of metabolic homeostasis remains largely unknown. Herein, we aimed to investigate the interplay between rhythmicity of host metabolism and gut microbiota-bile acid axis, as well as to assess the impact of obesity on them. We found that high fat diet feeding and Leptin gene deficiency (ob/ob) significantly disturbed the rhythmic patterns of insulin sensitivity and serum total cholesterol levels. The bile acid profiling unveiled a conspicuous diurnal rhythm oscillation of ursodeoxycholic acid (UDCA) in lean mice, concomitant with fluctuations in insulin sensitivity, whereas it was absent in obese mice. The aforementioned diurnal rhythm oscillations were largely desynchronized by gut microbiota depletion, suggesting the indispensable role of gut microbiota in diurnal regulation of insulin sensitivity and bile acid metabolism. Consistently, 16S rRNA sequencing revealed that UDCA-associated bacteria exhibited diurnal rhythm oscillations that paralleled the fluctuation in insulin sensitivity. Collectively, the current study provides compelling evidence regarding the association between diurnal rhythm of insulin sensitivity and gut microbiota-bile acid axis. Moreover, we have elucidated the deleterious effects of obesity on gut microbiome-bile acid metabolism in both the genetic obesity model and the diet-induced obesity model.
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