e have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4-6 weeks. In this study, rats were fed diets containing 32% stearic (STEAR) or palmitic (PALM) acid, and behavior, metabolic profile, and cell signals were compared with those of rats fed a matched low fat (11% fat [LF]) diet. Rats fed STEAR or PALM increased sucrose motivation relative to LF rats (one-way ANOVA for lever presses, p=.03). Diet did not change fasting glucose, insulin, total cholesterol, triglycerides, intravenous glucose tolerance test glucose profile, percent body fat, or total kcal, although kcal as fat were increased (ANOVA p<0.05). Cell signals were assessed in rats ranked from high to low sucrose motivation. Diet did not alter Thr- and Ser-phosphorylation of Akt in the medial hypothalamus (HYP) and striatum (STR). However, Ser-phosphorylation of GSK3B was decreased in HYP and STR from both High- and Low-Performer tertiles of STEAR and PALM rats (ANOVA within each brain region, p<0.05). Two Histone 3 (H3) modifications were also assessed. Whereas there was no effect of diet on the transcription-repressive H3 modification, H3K27me3, the transcription-permissive H3 modification, H3K4me3, was significantly decreased in the HYP of High-Performers fed PALM or STEAR (ANOVA p=.013). There was no effect of diet on H3K4me3 levels in HYP of Low-Performers, or in STR. Our findings suggest signal-specific and brain region-specific effects of PALM or STEAR diets, and may link downstream signaling effects of GSK3B activity and H3 modifications with enhanced motivational behavior.
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