Figure 6. LIF induces a persistent decrease in body weight, adipose mass, and food intake in ob/ob mice.
(A–E) Chow-fed Lepob/J, ob/ob, mice (11-week-old males) were housed 4 mice per cage 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 48 days (treatment) and subsequently followed for another 29 days (posttreatment) without injections. Body weight (A), food intake (D and E), and ECHO MRI measurements of fat mass (B) and lean mass (C) were measured at the indicated time points for 77 days. Body weight, fat mass, and lean mass are shown relative to the average day 0 reference value for each respective cohort. The average values for body weight (A) at day 0 were 39.5, 39.5, and 39.3 g for the PBS-, rLIF-, and rLIF K159A–treated mice, respectively. The average values for fat mass (B) at day 0 were 20.1, 20.6, and 20.9 g for the PBS-, rLIF-, and rLIF K159A–treated mice, respectively. The average values for lean mass (C) at day 0 were 16.7, 15.8, and 16.5 g for the PBS-, rLIF-, and rLIF K159A–treated mice, respectively. (F) Chow-fed Lepob/J, ob/ob, mice (10-week-old males) were housed 3 mice per cage and treated with PBS or rLIF as above for the indicated time interval, and food intake was measured. Every 3 days, 3 mice from each cohort were sacrificed, followed by harvesting and processing of the hypothalamus as described in the Methods. Aliquots (30 μg/lane) of pooled hypothalamic cell lysate from 3 mice treated identically were subjected to IB analysis with the indicated antibodies as described in Methods. The unfilled circles represent the average food intake from the day the 3 mice from each cohort were sacrificed for hypothalamic processing. (A–F) Each value represents mean ± SEM (A–C) or dot plots with mean ± SEM (D–F) of 3 mice (F) or 4 mice (A–E). These results were confirmed in 2 (F) or 3 independent experiments (A–E). *P < 0.05, **P < 0.01, and ***P < 0.001 based on Student’s t test comparing rLIF-treated mice with PBS- or rLIF K159A–treated mice over the respective time interval (D–F) or P value based on use of Generalized Estimating Equation approach with rLIF-treated mice as the reference value (A–C).