Isocaloric high-fat diet decreases motivation in the absence of obesity

Objective: Obesogenic diets induce persistent changes in physical activity and motivation. It remains unclear whether these behavioral changes are driven by weight gain or exposure to obesogenic diets themselves. We investigated how exposure to a high-fat diet (HFD) in the absence of obesity affected physical activity, food motivation, and circadian patterns in mice. Methods; C57Bl6/J mice were given similar to 80% of their daily calories in an HFD, known as isocaloric feeding, along with ad libitum access to laboratory chow. Weekly weights, physical activity levels, circadian patterns, operant behavior, and peripheral blood metabolic markers were measured to determine how an isocaloric HFD affected behavior and physiology. Following this period, the same cohort was exposed to an ad libitum HFD to monitor changes in weight gain and physical activity. Results: An isocaloric HFD did not significantly increase weight or change physical activity levels. An isocaloric HFD decreased motivation for sucrose pellets but did not alter weight gain with ad libitum HFD exposure. Conclusions: An isocaloric HFD was associated with decreased motivation for sucrose, as observed in reports of rodent models of obesity. These findings suggest that exposure to an obesogenic diet, even in the absence of significant weight gain, can induce behavioral changes associated with obesity.