Removal of high-fat diet after chronic exposure drives binge behavior and dopaminergic dysregulation in female mice

Abstract

A significant contributor to the obesity epidemic is the overconsumption of highly palatable, energy dense foods. Chronic intake of palatable foods is associated with neuroadaptations within the mesocorticolimbic dopamine system adaptations which may lead to behavioral changes, such as overconsumption or bingeing. We examined behavioral and molecular outcomes in mice that were given chronic exposure to a high-fat diet (HFD; 12weeks), with the onset of the diet either in adolescence or adulthood. To examine whether observed effects could be reversed upon removal of the HFD, animals were also studied 4weeks after a return to chow feeding. Most notably, female mice, particularly those exposed to HFD starting in adolescence, demonstrated the emergence of binge-like behavior when given restricted access to a palatable food. Further, changes in dopamine-related gene expression and dopamine content in the prefrontal cortex were observed. Some of these HFD-driven phenotypes reversed upon removal of the diet, whereas others were initiated by removal of the diet. These findings have implications for obesity management and interventions, as both pharmacological and behavioral therapies are often combined with dietary interventions (e.g., reduction in calorie dense foods).

Switching Adolescent High-Fat Diet to Adult Control Diet Restores Neurocognitive Alterations

“…Indeed, alterations in sucrose preference and dopamine system function observed after 12 weeks of adolescent HF were partially reversed 1 month after removal of the diet (Carlin et al, 2016). Similarly, rats exposed to a HF and high sugar diet for 10 days (postnatal 22–32) showed a reduction in sucrose preference when tested immediately after diet exposure.…”

Psychological and Neurobiological Correlates of Food Addiction

“…There is also some neural evidence supporting food as an addiction because of observations of downregulation of reward circuitry and difficulties with top-down cognitive control (Blum et al, 2014; Stice, Spoor, Bohon, et al, 2008; Volkow et al, 2003, 1997). Furthermore, animal studies show evidence of withdrawal symptoms in rats when access to sucrose solutions is terminated, as well as binge-like eating and dopaminergic dysregulation after removal of a high-fat diet (Avena et al, 2008; Carlin et al, 2016; Colantuoni et al, 2002). Critics of the FA hypothesis discuss an inability to pinpoint the exact “substance” that is responsible for the neuroaddictive responses (Ziauddeen & Fletcher, 2013).…”

Persistent effects of obesity: a neuroplasticity hypothesis

“…148 Dopaminergic receptor gene expression levels (for D1R and D2R) were reported to be decreased in the VTA, NAc, and prefrontal cortex of overweight mice fed a HFD from adolescence to adulthood, 149 an effect that recovered in the VTA and the prefrontal cortex, but not the NAc, following 4 weeks of withdrawal from a HFD. 149 Further work that examined D2R binding at an earlier time point (3 weeks after HFD) showed an increase in D2R striatal binding in overweight mice fed a HFD, 150 suggesting a time-dependent effect of HFD on dopamine receptor expression. Protein homogenates of the NAc of rats fed a diet high in saturated fat for 8 weeks during adulthood showed increased D1R levels via western blot quantification, despite no difference in weight gain relative to controls, 75 suggesting that D1R mRNA translation may be differentially regulated depending on specific fat components of the diet, the age of exposure to HFD, or both.…”

“…[114][115][116] This disrupts normal synaptic plasticity in projections from the prefrontal cortex to the NAc. 160 The disruptions in dopamine release, binding, or reuptake seen in rodents fed a HFD [144][145][146][147]149,151 suggest a role for a HFD in altering D2R-dependent plasticity mechanisms 29 (Fig. 1B).…”