(A–F) Chow-fed Lepob/J, ob/ob, mice (11-week-old males) were housed individually and injected i.p. with 100 μl PBS in the absence or presence of rLIF or rLIF K159A at 80 μg/kg body weight twice daily for 18 days throughout the experiment. PBS- and rLIF K159A–treated mice were either fed ad libitum or pair fed to the food intake of rLIF-treated mice fed ad libitum. Food intake (A), body weight (B), and ECHO MRI measurement of fat mass (C) were measured at the indicated time points. Body weight and fat mass are shown relative to the average day 0 reference value for each respective cohort. The average values for body weight (B) at day 0 were 44.5, 47.0, and 46.3 g for the PBS-, rLIF-, and rLIF K159A–treated mice fed ad libitum, respectively. The average day 0 values of body weight for the PBS- and rLIF K159A–treated mice pair fed were 45.9 and 46.0 g, respectively. The average values for fat mass (C) at day 0 were 25.4, 24.0, and 24.0 g for the PBS-, rLIF-, and rLIF K159A–treated mice fed ad libitum, respectively. The average day 0 values of fat mass (C) for the PBS- and rLIF K159A–treated mice pair fed were 24.5 and 25.6 g, respectively. Each value represents mean ± SEM of 4 mice. These results were confirmed in 2 independent experiments. ***P < 0.001 based on Student’s t test or P value based on use of Generalized Estimating Equation approach comparing multiple groups over time with rLIF-treated mice as the reference value (A–C).