Free-choice high-fat diet alters circadian oscillation of energy intake in adolescent mice: role of prefrontal cortex.

PURPOSE: Our aim was to characterize the effect of an unfamiliar high-fat diet (HFD) on circadian feeding behaviour, plasma parameters, body weight (BW), and gene expression in the prefrontal cortex (PFC) of adolescent male mice. To this end, mice were allowed to consume a HFD during 48 h, but one group was allowed a free choice of HFD or normal chow (FC-HFD), while the other was restricted to a non-optional unfamiliar HFD feeding (NOP-HFD).

METHODS: Energy intake was monitored at 6-h intervals during 48 h. Mice cohorts were killed at 6-h intervals after 48-h dietary treatment, and PFC samples dissected for RT-PCR analysis.

RESULTS: Mice on the FC-HFD protocol avoided eating the standard chow, showed lower energy intake and lower BW increase than NOP-HFD mice. All animals with access to HFD exhibited nocturnal overeating, but diurnal hyperphagia was more prominent in the FC-HFD cohort. A robust increase in tyrosine hydroxylase (Th) gene expression was detected specifically during the light period of the circadian cycle in FC-HFD mice. In contrast, both protocols similarly up-regulated the expression of cytosolic malic enzyme (Me1), which is very sensitive to HFD.

CONCLUSION: Our data show that the PFC participates in driving motivational feeding during HFD-evoked hyperphagia and also suggest that sensory neural pathways might be relevant for the onset of eating disorders and overweight. Moreover, we have observed that animals that had the possibility of choosing between standard chow and HFD were more hyperphagic and specifically displayed an overexpression of the tyrosine hydroxylase gene.