Dynamic regional alterations in mouse brain neuronal activity following short-term changes in energy balance

Objective Knowledge of the functional contribution to energy homeostatic control by different brain areas is limited. This study employed a systematic approach to identify brain regions specifically influenced by a positive energy balance. Methods The c-fos expression was mapped throughout the mouse brain after varying durations (24 hours to up to 14 days) of high-fat diet (HFD) exposure or after reversal from a 7-day HFD to a chow diet. In parallel, the metabolic and behavioral impacts of these treatments were examined. Results A HFD elicited rapid and pronounced compensatory responses which were, however, insufficient to overcome the impact of the positive energy balance. Rapid and dynamic responses of c-fos expression throughout the brain were seen over the course of HFD exposure, with some regions showing linear-like responses and some regions exhibiting biphasic responses. The switch from HFD to chow resulted in metabolic compensations mitigating the effects of the negative energy balance and a heightened preference for sweet taste. Interestingly, this diet switch led to a significant c-fos activation in the lateral hypothalamus, an area unresponsive to HFD intervention. Conclusions Plasticity exists in the extended brain networks facilitating rapid adaptations dependent on energy availability. Knowledge of these critical control points may provide novel antiobesity treatment targets.