Obesity risk in African American women is determined by a diet-by-phenotype interaction

非裔美国女性的肥胖风险是由饮食与表型的相互作用决定的

• 批准号: 10397052
• 负责人: BARBARA A GOWER
• 金额: $ 63.19万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10397052
• 关键词: Acute; Adherence; Adipose tissue; African American; American; Animal Model; Blood; Body Composition; Body Weight; Body Weight decreased; Body fat; Body mass index; Caucasians; Characteristics; Clinical; Clinical Trials; Constitutional; Consumption; Data; Diet; Dual-Energy X-Ray Absorptiometry; Eating; Effectiveness; Endocrine; Energy Metabolism; European; Exercise Test; Exposure to; Fat-Restricted Diet; Fatty acid glycerol esters; Food; Glucose; Hepatic; Human; Indirect Calorimetry; Individual; Insulin; Intervention Studies; Lead; Maintenance; Measures; Metabolic; Methodology; Monitor; Obesity; Obesity associated disease; Palate; Participant; Patient Self-Report; Pattern; Phase; Phenotype; Physiological; Physiology; Predisposition; Prevalence; Prevention; Production; Publishing; Quality of life; Randomized; Randomized Clinical Trials; Research Design; Resistance; Rest; Role; Satiation; Testing; Thinness; Time; Urine; Weight; Woman; clinical care; clinical practice; dietary; doubly-labeled water; effectiveness outcome; efficacy outcomes; evidence base; feeding; follow-up; genetic manipulation; improved; innovation; insulin secretion; insulin sensitivity; metabolic phenotype; metabolic rate; novel; obesity risk; obesity treatment; oxidation; personalized medicine; preservation; prevent; prospective; racial difference; racial disparity; response; total energy expenditure

Summary African-American (AA) women are disproportionately burdened by obesity. Our published data have led to the provocative hypothesis that this disparity has physiologic underpinnings. Specifically, AA women are characterized by a high acute insulin secretory response to a glucose challenge, as well as reduced hepatic insulin extraction, which together lead to postprandial circulating insulin concentrations that can be several fold higher than those observed in Caucasian (European-American, EA) women. The lipogenic actions of insulin could favor partitioning of energy to adipose tissue at the expense of ATP (energy) production. In fact, AA women have lower energy requirements than EA women, and are more energetically efficient. High insulin secretion, however, is only one factor that determines insulin action; another major factor is insulin sensitivity. Our data have shown that over time, weight (fat) gain in obesity-prone AA women is higher in those who are more insulin sensitive, whereas “obesity-resistant” (constitutionally lean) AA women have relatively lower insulin sensitivity. Our data also suggest that the lipogenic actions of insulin in AA women are exacerbated by a high-glycemic diet, which promotes insulin secretion. Finally, our data have shown that over time weight (fat) gain in AA women is predicted by the combination of insulin sensitivity and dietary glycemic load. Taken together, these observations suggest that many AA women are predisposed to obesity by their endocrine make-up, and that this predisposition is exacerbated by a high-glycemic diet. A natural corollary of this hypothesis is that for implementation of intentional weight loss, a low- (vs high-) glycemic diet will promote greater loss of body fat, and will enable successful weight loss maintenance by increasing energy expenditure. This corollary is supported by our preliminary data that indicate a 50% greater loss of fat with low- vs high-glycemic diet under controlled conditions in AA women. The project proposed herein will test these hypotheses through a randomized clinical weight loss trial of high- vs low-glycemic diets in obese AA women. The study has both an efficacy phase (controlled feeding during weight loss) to probe physiologic mechanisms (energy expenditure, metabolic efficiency), and an effectiveness phase (6-month free-living follow-up) to test the hypothesis that the low-glycemic diet will be more effective at promoting weight loss maintenance due in part to improved adherence and quality of life, and ease of implementing the diet. This study is innovative in that it proposes to test a specific physiologic mechanism that may underlie propensity to obesity; it includes both efficacy and effectiveness outcomes; it involves both quantitative and qualitative methodology; and it tackles optimization of both weight loss and weight loss maintenance. This study is intended to provide the evidence base necessary to improve the clinical care approach to weight loss.

概括 非裔美国 (AA) 女性承受着不成比例的肥胖负担。我们公布的数据有 导致了一个令人兴奋的假设，即这种差异具有生理基础。具体来说，AA 女性是 其特点是对葡萄糖挑战的高度急性胰岛素分泌反应，以及肝功能降低 胰岛素提取，共同导致餐后循环胰岛素浓度可增加数倍 高于白种人（欧美，EA）女性中观察到的水平。胰岛素的脂肪生成作用 可能有利于将能量分配给脂肪组织，但会牺牲 ATP（能量）的产生。事实上，AA 与 EA 女性相比，女性的能量需求更低，并且能量效率更高。高胰岛素 然而，分泌只是决定胰岛素作用的因素之一。另一个主要因素是胰岛素敏感性。 我们的数据显示，随着时间的推移，有肥胖倾向的 AA 女性的体重（脂肪）增加量高于那些有肥胖倾向的 AA 女性。 胰岛素敏感性更高，而“抗肥胖”（体质偏瘦）的 AA 女性则相对较低 胰岛素敏感性。我们的数据还表明，AA 女性中胰岛素的脂肪生成作用会因以下因素而加剧： 高血糖饮食，促进胰岛素分泌。最后，我们的数据表明，随着时间的推移，体重（脂肪） AA 女性的体重增加是通过胰岛素敏感性和膳食血糖负荷的结合来预测的。采取 总之，这些观察结果表明，许多 AA 女性由于她们的身材而容易肥胖。 内分泌构成，并且高血糖饮食会加剧这种倾向。一个自然的 该假设的推论是，为了实现有意识的减肥，低（与高）血糖饮食 将促进更多的身体脂肪减少，并通过增加能量来成功维持减肥 支出。我们的初步数据支持了这一推论，该数据表明，使用以下产品可减少 50% 的脂肪 AA 女性在受控条件下的低血糖饮食与高血糖饮食。本文提出的项目将测试 这些假设是通过一项针对肥胖 AA 患者的高血糖饮食与低血糖饮食进行的随机临床减肥试验得出的 女性。该研究有一个功效阶段（减肥期间控制喂养）来探讨生理学 机制（能量消耗、代谢效率）和有效性阶段（6 个月自由生活） 后续）来检验低血糖饮食在促进减肥方面更有效的假设 维持饮食的部分原因是提高了依从性和生活质量，并且易于实施饮食。这 这项研究的创新之处在于它提出测试可能是倾向的特定生理机制 肥胖;它包括功效和有效性结果；它涉及定量和定性 方法论；它解决了减肥和减肥维持的优化问题。这项研究是 旨在提供改善减肥临床护理方法所需的证据基础。