Figure 6. Insulin inhibits cell-autonomous leptin secretion.

(A) Serum leptin levels of 14-week-old Control^Δper (n = 18) and IR^Δper mice (n = 18) over a period of 30 days. Values are mean ± SEM. **P ≤ 0.01, ***P ≤ 0.001 versus control. (B) Serum leptin levels of 14-week-old Control^Δwb (n = 5) and IR^Δwb mice (n = 5) over the course of 30 days. Values are mean ± SEM. *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001 versus control. (C) Serum leptin levels correlated with epigonadal fat pad weight of 14-week-old Control^Δper (black bar; n = 17), IR^Δper (white bar; n = 13), Control^Δwb (dark gray bar; n = 13), and IR^Δwb mice (light gray bar; n = 6). Concentrations were measured 30 days after start of tamoxifen or doxycycline administration. Values are mean ± SEM. *P ≤ 0.05 versus control. (D) Serum adiponectin levels of 14-week-old Control^Δper (black bar; n = 13), IR^Δper (white bar; n = 8), Control^Δwb (dark gray bar; n = 13), and IR^Δwb mice (light gray bar; n = 18). Samples were taken 30 days after start of tamoxifen or doxycycline administration. Values are mean ± SEM. ***P ≤ 0.001 versus control. (E) Serum adiponectin levels correlated with epigonadal fat pad weight of 14-week-old Control^Δper (black bar; n = 13), IR^Δper (white bar; n = 10), Control^Δwb (dark gray bar; n = 13), and IR^Δwb mice (light gray bar; n = 16). Samples were taken 30 days after start of tamoxifen or doxycycline administration. Values are mean ± SEM. *P ≤ 0.05; *P ≤ 0.001 versus control. (F) General scheme for the effects of insulin resistance on circulating leptin and adiponectin levels. As a result of the loss of peripheral IR signaling, leptin and adiponectin secretion is disinhibited, resulting in an increase in circulating concentrations, still detectable in the raised leptin levels of IR^Δper mice. However, in IR^Δwb mice this effect is masked by a dramatic reduction in WAT mass.