We have reported that motivation for sucrose is increased in rats fed a moderate (31%) mixed-fat diet for 4-6 wk. 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 diet (LF; 11% fat) diet. Rats fed STEAR or PALM increased sucrose motivation relative to LF rats (one-way ANOVA for lever presses; P = 0.03). Diet did not change fasting glucose, insulin, total cholesterol, triglycerides, intravenous glucose tolerance test glucose profile, percent body fat, or total kilocalories, although kilocalories 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 GSK3Β 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. Although 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 = 0.013). 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 GSK3Β activity and H3 modifications with enhanced motivational behavior.
Keywords: GSK3β; food reward; high-fat diet; histone 3.