The Beneficial Effects of Apical Sodium‐Dependent Bile Acid Transporter Inactivation Depend on Dietary Fat Composition

Scope The apical sodium-dependent bile acid transporter (ASBT, SLC10A2) is important in the enterohepatic cycling of bile acids and thereby in the intestinal absorption of lipids. ASBT inhibition has been shown to improve aspects of the metabolic syndrome, but the underlying mechanisms have remained unclear. Here we investigated the effect of ASBT inhibition on the uptake of specific fatty acids and its consequences for diet-induced obesity and non-alcoholic fatty liver disease (NAFLD). Methods Intestinal fat absorption was determined in mice receiving an ASBT inhibitor and in Asbt-/- mice. Metabolic disease development was determined in Asbt-/- mice receiving a low fat control diet or high fat diet (HFD) rich in saturated fatty acids (SFAs) or PUFAs. Results Both ASBT inhibition and Asbt gene inactivation reduced total fat absorption, particularly of SFAs. Asbt gene inactivation lowered bodyweight gain, improved insulin sensitivity and decreased the NAFLD activity score upon feeding a HFD rich in SFAs but not in PUFAs. Conclusions The beneficial metabolic effects of ASBT inactivation on diet-induced obesity depend on decreased intestinal absorption of SFAs, and thus on the dietary fatty acid composition. These findings highlight the importance of dietary fatty acid composition in the therapeutic effects of ASBT inhibition. This article is protected by copyright. All rights reserved.