ENERGY METABOLISM IN THE POST OBESE STATE

肥胖后状态的能量代谢

• 批准号: 6306070
• 负责人: ERIC T. POEHLMAN
• 金额: $ 3.29万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6306070
• 关键词: basal metabolism; beta adrenergic receptor; bioenergetics; clinical research; female; genetic polymorphism; genetic regulation; genetic susceptibility; human middle age (35-64); human subject; obesity; weight loss

Significance/Aims. Obesity is characterized by increased body fat and propensity to numerous obesity-related illnesses, including hypertension, type II diabetes, cardiovascular, pulmonary and gallbladder disease, as well as some forms of cancer. The molecular basis of obesity in women is unknown. Obesity results from a positive energy balance. An individual may become obese with a normal rate of energy expenditure when intake is excessive, or with a normal level of food intake if energy expenditure is low. A low energy expenditure could be due to a metabolic defect or to hormonal abnormalities that are inherited. A novel polymorphism (TGGTrp --> CGGArg; codon 64) in the b3-adrenergic receptor gene was recently detected in a number of ethnic populations. The b3-adrenergic receptor is thought to play an important role in the regulation of energy expenditure and lipolysis. Subjects who harbor the polymorphism, tend to have a lower resting metabolic rate, higher body mass index and earlier onset of type II diabetes. Little is known, however, regarding the possible metabolic role of the b3-adrenergic receptor polymorphism as a contributor to low levels of energy expenditure that lead to obesity in older women. Our overall hypothesis is that the inherited polymorphism in the b3-adrenergic receptor gene contributes to the genetic basis of obesity via low levels of energy expenditure and fat metabolism in older women. Approach. Moderately obese women (50-65 y) who are homozygous or heterozygous for the b3-adrenergic receptor polymorphism will be weight-reduced, metabolically stabilized and compared to weight-reduced controls. We hypothesize that use of a post-obese model will unmask differences in energy expenditure that would otherwise be obscured by the obese state. Total daily energy expenditure, resting metabolic rate, the thermic effect of a meal, free-living physical activity, and fat metabolism will be compared among genotypes after weight reduction. These studies will help define the metabolic consequences of the b33-adrenergic receptor gene polymorphism in the regulation of daily energy expenditure and fat metabolism in older women.

意义/目标。 肥胖症的特征是体内脂肪的增加和对许多与肥胖相关疾病的倾向，包括高血压，II型糖尿病，心血管，肺和胆囊疾病以及某些形式的癌症。女性肥胖的分子基础尚不清楚。肥胖是由正能量平衡引起的。当摄入量过高时，一个人可能会以正常的能量消耗率肥胖，如果能量消耗较低，则可以使用正常的食物摄入水平。低能量消耗可能是由于代谢缺陷或遗传的激素异常。最近在许多种族种群中检测到了B3-肾上腺素能受体基因中一种新型的多态性（TGGTRP-> CGGARG； CODON 64）。人们认为B3-肾上腺素能受体在能量消耗和脂肪分解的调节中起着重要作用。拥有多态性的受试者往往具有较低的静息代谢率，更高的体重指数和更早的II型糖尿病发作。然而，关于B3-肾上腺素能受体多态性的代谢作用知之甚少，这是导致老年妇女肥胖的低能量消耗的原因。 我们的总体假设是，B3-肾上腺素能受体基因中的遗传多态性通过低水平的能量消耗和老年妇女的脂肪代谢有助于肥胖的遗传基础。方法。 对于B3-肾上腺素能受体多态性而纯合或杂合的中等肥胖女性（50-65岁）将减少体重，代谢稳定并与减轻体重减少对照组进行比较。我们假设使用后肥胖模型将揭露能量消耗的差异，否则肥胖状态会掩盖。减轻体重后的基因型中，将比较每日的总能量消耗，静息代谢率，餐食的热效应，自由生活的体育锻炼和脂肪代谢。这些研究将有助于定义B33-肾上腺素受体基因多态性在调节老年妇女的日常能量消耗和脂肪代谢中的代谢后果。