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

美国退伍军人的肥胖率特别高，给他们带来了巨大的健康负担。吃 行为是肥胖预防和管理的一个可能目标。因此，理解因素 随着肥胖率的持续上升，影响退伍军人的饮食行为将是重要的一步。一个关键 然而，理解这些因素的障碍是目前对基于性别的差异缺乏理解 在饮食行为上。基于性别的饮食行为差异是一贯观察。比如女性 比男性更有可能节食，对体重控制表示更大的关注， 健康饮食的重要性女性也报告了更多与饮食失调相关的行为， 肥胖率更高。男性和女性之间饮食行为和肥胖率的差异涉及 许多因素，如性腺激素，社会压力和规范，以及身体活动参与。 这些因素也与进食行为中涉及的神经元过程相互作用。对性有清晰的认识- 然而，食物摄入的神经机制的基础差异尚未建立。的 因此，本研究的目的是更好地了解性别差异如何影响享乐的神经生物学。 饮食行为。这与退伍军人的健康特别相关，因为妇女是增长最快的人口 退伍军人在VA接受医疗保健，近200万女性退伍军人。 了解食物摄入行为背后的神经生物学中基于性别的差异，以及如何 性腺激素有助于这些差异，将是重要的，为开发新的治疗方法， 超重/肥胖和体重维持。快乐饮食，或饮食超过自我平衡的需要，可能是 特别是与肥胖有关的疾病。因此，识别神经生物学中基于性别的差异， 享乐主义饮食尤其重要。为此，我们最近完成了一项初步研究， 基于性别的差异，神经元反应的食物高（与中性）享乐价值，在空腹和 联邦政府在禁食状态下观察到基于性别的差异，女性的反应更大 与男性相比，大脑中与食物有关的区域在丘脑和丘脑中起着突出的作用， 奖励处理这可能表明，女性对男性的显著和有益的方面更敏感， 比男性禁食时更能带来快感。当比较食物和非食物物体时，即，它 是具体的享乐与中性食物的比较，而不是作为一个整体的食物。 虽然这些初步调查结果具有启发性，但仍有许多问题有待回答， 处理。首先，由于样本量相对较小，初步研究的敏感性可能不足。 此外，在最初的调查中，所有女性都在月经周期的卵泡期进行扫描。 鉴于在月经的不同阶段观察到神经元对食物线索的反应不同， 因此，确定月经周期阶段如何影响基于性别的差异非常重要。此外，委员会认为， 在初步研究中不包括性腺激素的测量。这对于理解 激素对神经元对享乐食物反应的作用。最后，以前的研究没有 解决了神经元的差异如何转化为现实世界的行为，这将是至关重要的理解 两性之间的神经元差异如何指导治疗方案的发展。 本申请的总体目标是扩大初步调查结果，以更好地了解基于性别的 享乐饮食行为和食物奖励处理的神经生物学差异， 性腺激素有助于这些差异，以及这如何转化为现实生活中的饮食行为， 老兵

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.