(A) Body weight change (Δ) of adult female control (NTCP-heterozygous), NTCP-KO, TGR5-KO, and NTCP-TGR5–double KO (NTCP-TGR5–dKO) mice after a 15-week HFD (n = 6–14 per group). (B and C) WT and NTCP-KO mice (n = 5 per group) were fasted 4 to 5 hours, after which they received an i.p. injection with Poloxamer 407 (1 mg/kg) to inhibit lipoprotein lipase. At t = 0, mice were orally gavaged with olive oil containing tracer. Amounts of [3H]triolein and 3H activity in whole blood (B) and organs (C) were determined by liquid scintillation counting. Blood volume was estimated as 4.706% of total body weight. BAT, brown adipose tissue. (D) Per cage, 24-hour feces were collected from HFD-fed WT and NTCP-KO mice (n = 3–4 cages per group, 3–4 animals per cage), and remaining fecal calories were assessed by bomb calorimetry. (E and F) WT (n = 10) and NTCP-KO (n = 6) mice fed a HFD for 3 weeks were individually housed in fully automated calorimetric cages. Energy expenditure was calculated from O2 consumption and the resting energy requirement (E), and lean and fat mass were assessed by NMR (F). Error bars show ± SEM; each dot represents an individual animal. *P < 0.05, calculated by 1-way ANOVA (A) or Student’s t test (B and F).