Figure EV4. SH‐BC‐893 reduces food intake and triggers weight loss without toxicity.

• A, B
  Average energy expenditure using the Weir formula (A) or activity (B) from ZT12‐ZT24 in the mice from Fig 6A–D that were fed a HFD for 10 weeks and then treated with either vehicle (n = 8) or 120 mg/kg 893 (n = 6–8) by gavage on days 1 and 3.
• C–E
  Average daily distance run each day (C) or time spent on the wheel each day (D) or average daily time on wheels per mouse over the entire treatment period (E) in HFD‐fed mice gavaged with vehicle (n = 8) or 120 mg/kg 893 (n = 6) Mon/Wed/Fri for 4 weeks.
• F–I
  Relative (F,H) or absolute (G,I) fat (F,G) or lean (H,I) mass as measured by EchoMRI after 25 days of treatment in the mice shown in (C‐E) and Fig 6L–N; n = 6–10.
• J, K
  Daily food intake for the mice in Fig 6O–R. Mice were fed a chow diet or the HFD for 9‐10 weeks then gavaged with vehicle or 120 mg/kg SH‐BC‐893 Mon/Wed/Fri for 3 weeks; (n = 9). Average food intake per mouse in the 24 h after each of 8 different treatments (indicated with arrows) is shown; mice were euthanized 4 h after the ninth treatment. On day 6 in (J), the University Lab Animal Resources technician unexpectedly added food to the hopper and intake could not be accurately quantified (break in line).

Data information: In all panels, mean ± SEM shown. Using unpaired t‐tests (A, B, and E) or a one‐way ANOVA with Tukey’s correction (F‐I), *P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.001. In F and H, comparisons are made to HFD + vehicle (*), HFD + 120 mg/kg SH‐BC‐893 (#), or HFD + vehicle + wheel ($).