Rats (n = 8–10/group) were maintained on a low-fat diet (low fat), a HFS diet, or diet high in oleic acid (Oleic; see Table 2 for nutrient composition). Rats received i.c.v. infusions of 8 mU insulin or saline and food intake was measured at 24 hours. (A) Food intake after drug and saline (vehicle) control injections (*P < 0.05 compared with saline intakes). Rats maintained on low-fat, oleic acid, or HFS diet received an i.c.v. infusion of 8 mU insulin or saline and were sacrificed after 10 minutes. (B) Representative Western blots for p-AKT and GAPDH. (C) Densitometry analysis for all rats. ANOVA and post-hoc tests confirmed that rats maintained on HFS diet had lower p-AKT (P < 0.05 compared with other groups) and that only rats consuming low-fat and oleic acid diets exhibited insulin-induced p-AKT (*P < 0.05 compared with saline). (D) A separate group of rats were maintained on the same diets and received 10 μg i.c.v. leptin or saline (*P < 0.05 compared with saline). (E) Animals on the HFS-R diet (Table 1) were insulin resistant relative to the low-fat–fed animals, implying that the HFS diet, rather than increased body fat per se, is sufficient to reduce central insulin sensitivity. ANOVA and post-hoc tests confirmed only rats maintained on low-fat diet exhibited insulin-induced anorexia (data are mean ± SEM; *P < 0.05 compared with saline injection).