Dietary Regulation of FXR Deficiency

10 weeks age KK-Ay mice and C57BL/6J, homozygous FXR deficient (FXR^–/–) mice were maintained under environmentally controlled conditions with free access to standard chow diet and water as described previously28 (link). Animal experiments were conducted in the barrier facility of the Laboratory Animal Center, Xiamen University, approved by the Institutional Animal Use and Care Committee of Xiamen University, China, and the methods were carried out in accordance with the approved guidelines. Mice were fed with high fat diet containing 60% fat, 20% protein and 20% carbohydrate (Research Diets, D12492, New Brunswick, USA), and the food intake were measured every second day. Mice were i.p. injected with either vehicle (40% of 2-hydroxypropyl-β-cyclodextrin (HBC), Sigma, USA) or vehicle containing GW4064 (30 mg/kg, Sigma) or avermectin analogues (1.3 mg/kg) (International Laboratory, USA) once a day for 14 days. After 6 h fasting, mice were weighed and sacrificed. Livers were weighed and taken photos, and part of each liver was fixed in 4% paraformaldehyde. Liver histology characterization was analyzed by haematoxylin and eosin (H&E) staining with paraffin-embedded sections by standard procedures. Other tissues were collected and frozen in liquid nitrogen for use, and serums were collected to measure metabolite parameters.