Study On The Diurnal Rhythm Changes And Mechanisms Of Glucose And Lipid Metabolism And Related Bile Acids

Currently,obesity has become an increasingly serious public health problem.More and more studies have shown that obesity is accompanied by the disruption of the circadian rhythm of glucose and lipid metabolism,but the reasons for obesity disrupting this rhythm are not yet clear.To elucidate whether the gut microbiota-bile acid axis is involved in the disruption of circadian rhythms of glucose and lipid metabolism in obesity,we conducted glucose and lipid metabolism tests,bile acid profiles analysis and gut microbiota sequencing in mice fed low fat diet(LFD)and HFD and ob/m and ob/ob mice fed chow diet at ZT0 and ZT12.The results showed that insulin sensitivity in the control group of mice significantly increased at ZT12,and serum total cholesterol levels significantly decreased at ZT12.HFD and ob/ob disrupted the diurnal rhythm of insulin sensitivity and serum total cholesterol.Through analysis of bile acid profiles,we found that ursodeoxycholic acid(UDCA)exhibits significant circadian rhythm oscillations in serum,intestine,and cecum content of the control group(LFD and ob/m group).However,UDCA in the obese group lost circadian rhythm oscillations.There was a significant correlation between UDCA and serum fasting insulin,serum total cholesterol(TC),and homeostatic model assessment of insulin resistance(HOMA-IR).Finally,through gut microbiota clearance,we proved that gut microbiome is involved in the regulation of the diurnal rhythm oscillation of insulin sensitivity and serum total cholesterol.Analyzing the gut microbiota associated with UDCA,we found that the Turicibacter and Ruminococcaceae＿NK4A214 genera exhibit significant diurnal rhythm oscillation in LFD group,while their diurnal rhythm disappears in the obese group.Therefore,our research not only suggests the circadian rhythms and interactions between insulin sensitivity,UDCA,and gut microbiota but also provides evidence for improving the circadian rhythms of glucose metabolism and lipid metabolism in obese individuals by interfering with gut microbiota and bile acid.