Sex Effects on the Neurobiology of Eating Behaviors in Veterans with Overweight/Obesity

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The rate of obesity is particularly high in U.S. Veterans, conferring a substantial health burden. Eating behaviors are one possible target for obesity prevention and management. As such, understanding factors impacting eating behaviors in Veterans will be an important step as obesity rates continue to rise. A key obstacle in understanding these factors, however, is the current lack of understanding of sex-based differences in eating behaviors. Sex-based differences in eating behaviors are consistently observed. For example, women are more likely to diet than men, express greater concern about weight control, and attribute greater importance to healthy eating. Women also report more behaviors associated with eating disorders, and have higher rates of obesity. Differences in eating behaviors and obesity rates between men and women involve a number of factors, such as gonadal hormones, social pressures and norms, and physical activity engagement. These factors also interact with neuronal processes involved in eating behaviors. A clear understanding of sex- based differences in neuronal mechanisms underlying food intake has yet to be established, however. The goal of this proposal, therefore, is to better understand how sex differences impact the neurobiology of hedonic eating behaviors. This is particularly relevant to Veterans' health, as women are the fastest-growing population of Veterans receiving healthcare at the VA, with almost 2 million living women Veterans. Understanding sex-based differences in the neurobiology underlying food intake behaviors, and how gonadal hormones contribute to these differences, will be important for developing novel treatment methods for overweight/obesity and weight maintenance. Hedonic eating, or eating beyond homeostatic needs, may be particularly associated with obesity. As such, identifying sex-based differences in neurobiology underlying hedonic eating is of particular relevance. To this end, we recently completed a preliminary study investigating sex-based differences in neuronal responses to foods with high (vs. neutral) hedonic value, in both fasted and fed states. Sex-based differences were observed in the fasted state, with greater responses in women compared to men in the nucleus accumbens and insula, brain regions with prominent roles in food-related reward processing. This could indicate that women are more sensitive to salient and rewarding aspects of hedonic foods than men when fasted. This was not observed when comparing foods to non-food objects, i.e., it was specific to the comparison of hedonic to neutral foods, rather than foods as a whole. While these preliminary findings are provocative, many questions remain to be answered and issues addressed. First, the sensitivity of the initial study was likely insufficient, given the relatively small sample size. Additionally, women were all scanned in the follicular phase of the menstrual cycle in the initial investigation. Given that differences in neuronal responses to food cues are observed in different phases of the menstrual cycle, it is important to determine how menstrual cycle phase impacts sex-based differences. Furthermore, measures of gonadal hormones were not included in the preliminary study. This will be critical in understanding the contribution of hormones to neuronal responses to hedonic foods. Lastly, previous studies have not addressed how neuronal differences translate to real-world behaviors, which will be essential in understanding how neuronal differences between sexes can guide development of treatment options. The overall goal of this application is to expand on initial findings to better understand sex-based differences in the neurobiology underlying hedonic eating behaviors and food-based reward processing, how gonadal hormones contribute to these differences, and how this translates to real-life eating behaviors in Veterans.