Diet-induced obesity and weight loss alter bile acid concentrations and bile acid–sensitive gene expression in insulin target tissues of C57BL/6J mice

Abstract

Bile acids (BAs) influence the metabolism of glucose, lipids, and energy expenditure. We hypothesized that BA concentrations and related gene expression would be altered in lean (low-fat diet fed; LFD) vs diet-induced obese (high-fat diet fed; HFD) groups of mice and that some detected changes would remain after weight loss in an HFD group switched to the LFD (SW). Taurine conjugates dominated the bile acid composition of the liver, epididymal white adipose tissue (eWAT), and hypothalamus, with the latter having lower levels (~95%, ~95%, and ~80%, respectively; P<.05). Plasma conjugated bile acids were elevated in the HFD relative to the LFD and SW animals. Total hepatic BA concentrations decreased in obese mice fed HFD, and levels returned to preobese levels in the SW group. Subtle changes in unconjugated bile acids were detected in the eWAT, hypothalamus, and muscle. Liver expression of a variety of enzymes involved in BA synthesis (eg, Cyp27a1, Acox2), BA transport (eg, Slc22a8), and BA-sensitive receptors (Fxr, Tgr5) were unchanged by HFD feeding but decreased with SW. Other hepatic enzymes were induced in the SW group (eg, Amacr and Bal). In eWAT, Cyp27a1 and Acox2 also declined in the SW group, whereas the HFD group showed reduced expression of BA transporters (eg, Abcc3), and changes in Fxr and Tgr5 were unclear. Therefore, although most detectable changes in BA metabolism associated with diet-induced obesity are reversed by diet-induced weight loss, some effects on BA composition, concentrations, and gene expression can persist after weight loss.