Interactions of diet, exercise, metabolism, and weight change in humans

经过几天的体重维持饮食，20名肥胖的成年志愿者（BMI在30 - 40 kg/m2之间）将被纳入代谢临床研究单位（MCRU），并在基线饮食的额外5天后，他们的饮食将被修改，导致基线饮食脂肪减少85%或60%，在接下来的6天内减少基线饮食碳水化合物。这些饮食调整产生了相当的热量减少。主要结果测量将是在基线和低热量饮食阶段测量的代谢、大脑奖励回路和区域大脑活动对食物刺激的反应的变化。每次控制饮食后，我们将立即使用计算机自动售货机系统测量3天的自由摄食量。受试者将在2-10周洗脱期后返回MCRU，接受相反的低热量饮食。20名体重正常的对照受试者（BMI在18.5 - 25 kg/m2之间）将在平衡的体重维持饮食下测量大脑奖励回路和响应食物刺激的局部大脑活动。 在第二次住院访视后，所有肥胖受试者将立即被分配到12周门诊体重减轻计划，目标是实现至少5%的体重减轻。我们将调查住院期间测量的短期脂肪失衡与减肥计划期间体重和脂肪变化之间的关系。最后，我们将评估减肥对新陈代谢，大脑奖励回路和区域大脑活动的影响，以响应食物刺激。这项研究将导致更好地理解感知和响应负能量平衡的生理机制，无论是急性还是几周后，最终可能导致肥胖治疗的长期成功率提高。

After several days of eating a weight-maintenance diet, 20 obese adult volunteers (BMI between 30 - 40 kg/m2) will be admitted to the metabolic clinical research unit (MCRU) and, after 5 additional days of the baseline diet, their diets will be modified to result in either 85% reduction of the baseline dietary fat or a 60% reduction of the baseline dietary carbohydrate for the next 6 days. These diet modifications produce an equivalent caloric reduction. The primary outcome measurements will be changes of metabolism, brain reward circuitry and regional brain activity in response to food stimuli measured during the baseline and reduced calorie diet phases. Immediately following each controlled diet, we will measure 3 days of ad-libitum food intake using a computerized vending machine system. The subjects will return to the MCRU after a 2-10 week washout period to receive the opposite reduced calorie diet. Twenty control subjects with normal body weight (BMI between 18.5 - 25 kg/m2) will have measurements of brain reward circuitry and regional brain activity in response to food stimuli while on a balanced, weight-maintenance diet. Immediately following the second in-patient visit, all of the obese subjects will be assigned to a 12 week out-patient weight loss program with the goal of achieving at least 5% weight loss. We will investigate the relationship between short-term fat imbalances measured during the inpatient phases, and the body weight and fat changes during the weight loss program. Finally, we will evaluate the effects of weight loss on metabolism, brain reward circuitry, and regional brain activity in response to food stimuli. This study will result in an improved understanding of the physiological mechanisms that sense and respond to negative energy balance, both acutely and after several weeks, and may eventually lead to increased long-term success of obesity treatment.