DIETARY FAT, CARBOHYDRATE BALANCE AND WEIGHT MAINTENANCE

膳食脂肪、碳水化合物平衡和体重维持

• 批准号: 3231592
• 负责人: JEAN-PIERRE FLATT
• 金额: $ 19.16万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1997-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3231592
• 关键词: albino mouse; bioenergetics; body composition; calorimetry; dietary carbohydrates; dietary lipid; exercise; fat body; free fatty acids; glucocorticoids; hormone inhibitor; insulin; laboratory rat; lactation; nutrient intake activity; nutrition related tag; obesity; oxidation; pregnancy; pyruvates; weight control; weight control agent

When access to food is unrestricted, the constraint of having to oxidize a metabolic fuel mix containing as much fat as the diet plays a more important role in determining body fat than overall energy expenditure. The main goal of the proposed investigations is to test the implications of this concept in understanding the causes for the high incidence of obesity in affluent societies. Using a unique method to establish daily and cumulative carbohydrate and fat balances over many consecutive days, which combines 24-h respiratory gas exchange, food intake and spontaneous running activity measurements, we have demonstrated that weight maintenance in ad libitum fed mice is brought about by modulation of food intake, and that this serves primarily the need to maintain carbohydrate rather than energy balance. We now propose to determine whether this is the case in genetically obese mice as well, and whether dietary fat also raises their body fat content in a dose-dependent manner. To compare the effectiveness of low-fat diets in reversing obesity induced by high-fat diets, the changes in body fat content which they elicit will be followed using a new plethysmographic method for body density measurements in live animals. Next we propose to study whether variables known to influence body fat content, such as pregnancy, exercise, glucocorticoids or their antagonists, drugs and cold exposure, do so through their impact on the RQ and the carbohydrate economy, and thereby on food intake, and to which extent these effects may be influenced by the diet's fat content. In particular we will test the hypothesis that fat accumulation during pregnancy is due in part to the increment in food intake needed to compensate for the increasing amounts of glucose oxidized by the fetus, and that this accumulation may be altered by changing the diet's fat content. Whole-body considerations suggest that the opposing actions of insulin and FFA concentrations on pyruvate oxidation are likely to play a crucial role in limiting or promoting the development of obesity and that the usual influence of increases in the adipose tissue mass in restricting pyruvate oxidation fails to occur in cases of extreme obesity. To see how adjustment of pyruvate oxidation is brought about in vivo, the amounts of food provided to normal and genetically obese mice will be restricted, thereby forcing them to operate at the same average 24-h RQ. Comparisons of daily RQ patterns to assess carbohydrate dissipation after the feeding period, and measurements of glycogen levels and body fat content by chemical carcass analysis will be used to examine how the body composition of genetically obese animals has to differ to bring about appropriate restraint on pyruvate oxidation. These investigations will contribute to the body of knowledge from which dietary recommendations most susceptible to facilitate weight maintenance at lower levels of adiposity can be formulated.

当获取食物不受限制时， 一个代谢燃料混合物含有尽可能多的脂肪作为饮食发挥更大的作用， 在确定身体脂肪比整体能量消耗的重要作用。 拟议调查的主要目标是检验 这一概念在理解高发病率的原因， 富裕社会中的肥胖症。使用独特的方法建立每日 以及连续多天的累积碳水化合物和脂肪平衡， 它结合了24小时呼吸气体交换，食物摄入和自发性 通过活动测量，我们已经证明， 通过调节食物， 摄入量，这主要是为了维持碳水化合物的需要， 而不是能量平衡。我们现在建议确定这是否是 遗传性肥胖小鼠的情况也一样，以及膳食脂肪是否也 以剂量依赖的方式提高他们的体脂含量。比较 低脂饮食逆转高脂饮食诱导肥胖的有效性 饮食，他们引起的身体脂肪含量的变化将被跟踪 使用新的体积描记法测量活体中的身体密度 动物 下一步我们打算研究已知的影响身体脂肪的变量 内容，如怀孕，运动，糖皮质激素或其 拮抗剂、药物和冷暴露，通过它们对RQ的影响来实现 和碳水化合物经济，从而对食物摄入量， 这些影响可能会受到饮食中脂肪含量的影响。在 特别是，我们将测试的假设，脂肪积累期间 怀孕的部分原因是食物摄入量的增加， 弥补胎儿氧化葡萄糖的增加量， 这种积累可以通过改变饮食中的脂肪来改变 内容 全身考虑表明，胰岛素和 FFA浓度对丙酮酸氧化可能起着至关重要的作用 限制或促进肥胖的发展， 脂肪组织质量增加对限制丙酮酸的影响 在极度肥胖的情况下氧化不能发生。 为了了解丙酮酸氧化的调节是如何在 在体内，提供给正常和遗传性肥胖小鼠的食物量 将受到限制，从而迫使它们以相同的平均水平运行 24小时RQ。比较每日RQ模式以评估碳水化合物 摄食期后的消耗，以及糖原水平的测量 和身体脂肪含量的化学胴体分析将被用来检查 基因肥胖动物的身体组成如何不同， 对丙酮酸氧化产生适当的抑制。 这些调查将有助于丰富知识体系， 最容易促进体重维持的饮食建议 在较低水平的肥胖可以制定。