Figure 5. Enhanced Leptin Sensitivity in MyD88^ΔCNS Mice on High-Fat Diet.

A Changes in food intake after intraperitoneal leptin treatment in control (n= 7) and MyD88^ΔCNS (n=7) mice on high-fat diet at the age of 14 weeks. Data represent daily food intake after a 3-day treatment with twice-daily injections of saline or 2 mg/kg leptin.

B Upper panel: Western blot analysis of phosphorylated STAT3 and STAT3 in dissected arcuate nuclei of 16-week-old control (n= 5) and MyD88^ΔCNS (n=5) mice, which were intravenously injected with either saline or leptin and sacrificed 30 minutes after the injection. Lower panel: Densitometrical analysis of phosphorylated STAT3 of leptin injected mice (n=4) as compared to mice injected with saline (n=1).

C pSTAT3 immunohistochemistry of ARC neurons of control and MyD88^ΔCNS mice on normal chow diet (NCD) or high-fat diet (HFD) was performed in overnight-fasted animals, which were intraperitoneally injected with either saline or leptin and sacrificed 30 min after stimulation. Arrows indicate neurons positive for pSTAT3 in each panel. Blue (DAPI), DNA; green, pSTAT3.

D Upper panel: Average body weight of female control and MyD88^ΔCNS mice on HFD (n=7–11) at the age of 5 weeks. Lower panel: Lean mass and body fat content of female control and MyD88^ΔCNS mice on HFD (n=7–11) at the age of 5 weeks as measured by nuclear magnetic resonance.

E Changes in food intake after intraperitoneal leptin treatment in control (n=4) and MyD88^ΔCNS (n=3) mice on high-fat diet at the age of 5 weeks. Data represent daily food intake after a 3-day treatment with twice-daily injections of saline or 2 mg/kg leptin.

F Upper panel: Western blot analysis of phosphorylated STAT3 and STAT3 in dissected arcuate nuclei of 10-week-old control (n=7) and MyD88^ΔCNS (n=3) mice, which were ICV injected with palmitate (66pmol) 30 minutes prior to ICV injection of leptin (500ng). Lower panel: Densitometrical analysis of phosphorylated STAT3 of Palmitate + Leptin injected MyD88^ΔCNS mice (n=3) as compared to Palmitate + Leptin injected control mice (n=7).

G Male control (n=9) and MyD88^ΔCNS (n=9) mice on HFD were intraperitoneally injected at the onset of the dark cyle with saline or MTII at the age of 13 weeks. Cumulative food intake and body weight were measured 2, 4, and 24 h after injection.

Displayed values are means ± S.E.M.; *, p ≤ 0.05; **, p ≤ 0.01; ***, p ≤ 0.001.