Chronic high fat diet changes gene expression within the brain reward system: critical periods and sex differences

Abstract

Both the overconsumption of palatable foods and chronic drug use can result in a state of “reward hypofunction”. Previously, we have shown that chronic consumption of a high fat (HF) diet in mice alters dopaminergic and opioid gene expression within the central reward circuitry in a pattern consistent with reward hypofunction. The goal of the present study was to examine whether animals exposed during early life, adolescence or as adults would differ in their responsiveness to the high fat diet, with the prediction that early life exposure would be more potent. Three groups of mice were fed HF diet at birth, 3 weeks, or 6 weeks of age (n=6/group). After 12 weeks, target gene expression was measured in the ventral tegmental area, nucleus accumbens and prefrontal cortex. Contrary to our hypothesis, adult exposure and early exposure to the HF diet both altered gene expression within the central reward circuitry. The pattern of changes differed across regions and timepoints and varied by sex in important ways. The functional implications of these differences will be presented. In sum, we identified changes in the reward circuitry in response to HF diet exposure that parallel neuroadaptations seen in chronic drug use. These changes occur with both early life and adult exposure to HF diet, and vary by sexFunding to TMR: MH087978, MH091372