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 非裔美国人（AA）妇女因肥胖而被不成比例地燃烧。我们发布的数据有 导致了挑衅性的假设，即这种差异具有生理基础。具体来说，女性是 以高急性胰岛素分泌对葡萄糖挑战的反应以及肝脏降低的特征 胰岛素提取，共同导致餐后循环胰岛素浓度，可能是几倍 高于白人（欧美，EA）妇女中观察到的那些。胰岛素的脂肪生成作用 可以以ATP（能量）生产为代价将能量分配给脂肪组织。实际上，AA 女性的能量需求低于EA女性，并且在精力充沛的效率上。高胰岛素 但是，分泌只是决定胰岛素作用的一个因素。另一个主要因素是胰岛素敏感性。 我们的数据表明，随着时间的流逝，容易肥胖的AA女性的体重（脂肪）在 胰岛素更敏感，而“抗肥胖症”（宪法上的瘦身）妇女的妇女相对较低 胰岛素灵敏度。我们的数据还表明，胰岛素在AA女性中的脂肪生成作用被加剧 一种高血糖饮食，可促进胰岛素分泌。最后，我们的数据表明随着时间的重量（脂肪） 通过胰岛素敏感性和饮食血糖负荷的组合可以预测AA女性的增益。拍摄 总之，这些观察结果表明，许多AA妇女被其肥胖症偏爱 内分泌的构成，这种易感性通过高血糖饮食加剧。自然 该假设的基督教育是为了实施故意体重减轻，低 - （vs高）血糖饮食 将促进更大的体内脂肪损失，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种推论，该数据表明， 在AA妇女的受控条件下，低血糖饮食与高血糖饮食。本文提出的项目将测试 这些假设通过肥胖的高VS低血糖饮食的随机临床减肥试验 女性。该研究既有有效的阶段（在减肥期间受控喂养）来探测生理 机制（能量消耗，代谢效率）和有效阶段（6个月的自由生活 随访）以检验低血糖饮食在促进体重减轻的假设 维护部分是由于改善的依从性和生活质量以及易于实施饮食的易变性。 研究具有创新性，因为它提出了测试特定生理机制，该机制可能是基础的 肥胖;它包括有效性和有效性结果；它涉及定量和定性 方法论；它可以解决体重减轻和减肥维持的优化。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。