282: Maternal obesity-associated reduction in offspring mesolimbic dopamine signaling correlates with sex-specific overeating and obesity risk

We have previously shown that maternal diet-induced obesity (MATOB) is associated with decreased dopamine release in the mesolimbic reward circuit across the lifespan, with persistent deficits in female (F) offspring only. Diminished dopamine in the mesolimbic circuit is associated with addictive/reward-seeking behaviors. We sought to determine whether the sex differences observed in mesolimbic dopamine were associated with increased reward-based (hedonic) eating and obesity liability in MATOB-exposed offspring, with Fs more vulnerable. C57Bl/6J dams were assigned to a 60% high-fat or 10% fat control diet (CD) for 14 weeks pre-breeding and during pregnancy/lactation. Male (M) and F offspring were weaned at 3.5 weeks to CD. 15-30 offspring/sex/diet group were evaluated for all experiments. Hedonic eating was evaluated in adolescent (8wk) MATOB and CD offspring with palatable food and liquid consumption tests (peanut butter and chocolate beverage). Usual food consumption and metabolic rate were quantified in adult offspring using metabolic cages. Weekly weight gain was quantified from weaning to adulthood, and adult body composition was determined with EchoMRI. F but not M MATOB adult offspring were significantly heavier with significantly increased body fat percentage compared to sex-matched controls (Fig 1A/B). Metabolic rate was not significantly different between MATOB and CD adult offspring (Fig 1C). F offspring had both significantly increased hedonic eating (Fig 2A) and usual food consumption compared to sex-matched controls and MATOB Ms, respectively (Fig 2B). Patterns of hedonic eating differed by offspring sex (Fig 2A). F offspring have increased vulnerability to obesity when exposed to MATOB in utero. Together with our prior finding of persistently reduced mesolimbic dopamine release in F MATOB offspring only, these data suggest that reduced dopamine release may program F offspring to overeat, leading to a sex-biased increase in obesity risk. Future studies will focus on mesolimbic dopamine signaling as a therapeutic target to reduce offspring obesity.View Large Image Figure ViewerDownload Hi-res image Download (PPT)