Hyperglycemia exacerbates dyslipidemia-induced changes in uptake, synthesis, and transporters of bile acids in rats: Assessment of restorative potentials of ALA and EPA plus DHA

In this study, under dyslipidemia (D) and dyslipidemia with diabetes (DD) conditions, we assessed the intestinal bile acid (BA) uptake, BA transporter expression and de novo BA synthesis in rats. The restorative potentials n-3 fatty acids [{alpha-linolenic acid (ALA), DD + canola oil (CNO)} and eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA), DD + fish oil (FO)} were also assessed. DD group had significantly (p < 0.05) increased intestinal BA uptake and Asbt and Osta/b mRNA expression, increased serum BA level, decreased hepatic Ntcp, Bsep and Cyp7a1 mRNA expression, increased hepatic HMG-CoA reductase activity, increased hepatic Fxr and Shp mRNA expression, decreased hepatic Lrh-1 and Hnf4a mRNA expression and decreased fecal BA level, when compared to control, D, DD + CNO, and DD + FO group. Our data show for the first time that, hyperglycemia exacerbates dyslipidemia-induced dysregulation of BA metabolism and transport. Dietary EPA + DHA exhibited superior effect than ALA in normalizing dyslipidemia and hyperglycemia-induced disturbances.