Figure 1. NTCP-KO mice have attenuated body weight gain and reduced (hepatic) adiposity when fed a high-fat diet.

(A) Conjugated and unconjugated plasma bile acid levels, measured by high-performance liquid chromatography (HPLC), of nonfasted, chow-fed NTCP-expressing (^+/–) and NTCP-KO mice (n = 8). conj., conjugated; unconj., unconjugated. (B–G) Female wild-type (WT, n = 10) or NTCP-KO (n = 13) mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 16 weeks. (B) Concentration of the individual conjugated and unconjugated bile acid species in plasma. Plasma was collected after a 4-hour fast, and bile acid concentration and species were measured by HPLC. N.D., not determined. Asterisk indicates significant changes of both HFD groups compared with the WT LFD group; hash tag indicates a significant change between NTCP-KO HFD and WT HFD mice. (C) Body weight change (Δ) and (D) body weight accumulation between the start and end of the experiment. (E) Food intake g/day per animal. Food intake per cage was weekly measured, divided over the number of animals per cage, and averaged for the 16-week period. n = 3 or 4 cages per group, each with 3 or 4 animals per cage. (F) Hepatic triglyceride content by representative images of liver histology by H&E (top) and Oil Red O (ORO, bottom) staining. Digital images were taken by using a ×10 eyepiece and a ×20 objective. (G) Plasma biochemistry displaying levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk. Phos.), and lactate dehydrogenase (LDH). All data are represented as mean ± SEM; each dot represents an individual animal (A–D and G) or cage (E). *P < 0.05, calculated with 2-way ANOVA (Holm-Šídák’s) (A) or 1-way ANOVA (Tukey’s) (B–E and G).