Correlation between 12α-hydroxylated bile acids and insulin secretion during glucose tolerance tests in rats fed a high-fat and high-sucrose diet

Abstract

Background Previously, we found a significant relationship in a rat study between energy intake and bile acid (BA) metabolism especially 12α-hydroxylated (12αOH) BAs. The present study was designed to reveal relationships among BA metabolism, glucose tolerance, and cecal organic acids in rats fed a high-fat and high-sucrose diet (HFS) by using multivariate and multiple regression analyses in two types of glucose tolerance tests (GTTs). Methods Male WKAH/HkmSlc rats were fed with a control or a HFS for 13 weeks. Oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT) were performed at week 9 and 11, respectively. BAs were analyzed by using ultra high-performance liquid chromatography-mass spectrometry. Organic acid concentrations in cecal contents were analyzed by using ultra high-performance liquid chromatography with post-column pH buffered electric conductivity method. Results A positive correlation of aortic 12αOH BA concentration was observed with energy intake and visceral adipose tissue weight. We found that an increase of 12αOH BAs in enterohepatic circulation, intestinal contents and feces in the HFS-fed rats compared to those in control rats regardless of no significant increase of total BA concentration in the feces in the test period. Fecal 12αOH BA concentration was positively correlated with maximal insulin level in OGTT and area under curve of insulin in IPGTT. There was a positive correlation between aortic 12αOH BAs concentration and changes in plasma glucose level in both OGTT and IPGTT. In contrast, a decrease in the concentration of organic acids was observed in the cecal contents of the HFS-fed rats. Multiple linear regression analysis in the IPGTT revealed that the concentrations of aortic 12αOH BA and cecal acetic acid were the predictors of insulin secretion. Moreover, there was a positive correlation between concentration of portal 12αOH BAs and change in insulin concentration of peripheral blood in the IPGTT. Conclusion The distribution analysis of BA compositions accompanied by GTTs revealed a close relationship between 12αOH BA metabolism and insulin secretion in GTTs in rats.

12α-Hydroxylated bile acid enhances accumulation of adiponectin and immunoglobulin A in the rat ileum

“…A high-energy supply from diet enhances the production of 12αOH BA in the body. Such an increase in 12αOH BAs is frequently observed in mice 3 , rats 4 , 5 , and humans 6 .…”

“…Those suggests that there was no apparent negative feedback inhibition in BA synthesis 20 . This CA-supplementation may mimic conditions such as increased 12αOH BA in obesity or a high-energy consumption in rats without inhibition of BA synthesis 4 , 5 .…”

Quantitative proteomics study of carnosine effect in an animal model of Western diet‐induced nonalcoholic fatty liver disease

“…The test response was expressed as the area under the curve (AUC), calculated by the trapezoidal method (total AUC). [ 26 ]…”

Dietary Supplementation with Cholic Acid Reduces Insulin Secretion in Response to Intraperitoneal Glucose Administration in Rats

“…Also, the plasma levels of 12-hydroxylated BAs are associated with insulin resistance in humans (8). In our previous study, a positive correlation was observed between insulin secretion and portal 12-hydroxylated BA concentration in high-fat and high-sucrose diet-fed rats in an intraperitoneal glucose tolerance test (IPGTT) (9).…”

“…Higher energy consumption enhances gains in not only body weight but also white adipose tissue weight in high-fat and high-sucrose diet-fed rats compared to the control in rats (9). The CA-fed rats mentioned before are an appropriate model to investigate the direct effect of 12-hydroxylated BAs on insulin secretion in vivo because there is no difference in dietary energy consumption and body weight (6).…”