DIETARY FAT, CARBOHYDRATE BALANCE AND WEIGHT MAINTENANCE

膳食脂肪、碳水化合物平衡和体重维持

基本信息

批准号：
2458738
负责人：
JEAN-PIERRE FLATT
金额：
$ 22.03万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-07-01 至 1999-07-31
项目状态：
已结题

项目摘要

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，必须氧化的限制含有与饮食一样多的脂肪的代谢燃料混合物发挥了更大的作用在决定身体脂肪方面比总体能量消耗更重要。拟议调查的主要目标是测试其影响这个概念在理解高发病率的原因时富裕社会的肥胖。用独特的方法建立日常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、食物摄入和自发跑步活动测量，我们已经证明体重随意喂养的小鼠的维持是通过食物的调节来实现的摄入量，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是如此，以及膳食脂肪是否也以剂量依赖性方式增加体内脂肪含量。为了比较低脂饮食对逆转高脂引起的肥胖的有效性饮食，它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进行现场身体密度测量动物。接下来我们建议研究已知的变量是否会影响身体脂肪内容，例如怀孕、运动、糖皮质激素或其拮抗剂、药物和寒冷暴露，通过它们对 RQ 的影响来实现这一点和碳水化合物经济，从而影响食物摄入量，以及这些影响在一定程度上可能受到饮食中脂肪含量的影响。在特别是我们将检验以下假设：怀孕的部分原因是由于需要增加食物摄入量补偿胎儿氧化的葡萄糖量的增加，并且可以通过改变饮食中的脂肪来改变这种积累内容。全身考虑表明胰岛素和胰岛素的相反作用 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以及通常的脂肪组织量增加对限制丙酮酸的影响在极度肥胖的情况下，氧化不会发生。了解丙酮酸氧化的调节是如何进行的体内，提供给正常和遗传性肥胖小鼠的食物量将受到限制，从而迫使他们以相同的平均水平运营 24 小时 RQ。比较每日 RQ 模式以评估碳水化合物饲喂期后的消散和糖原水平的测量通过胴体化学分析来检测身体脂肪含量遗传性肥胖动物的身体成分有何不同对丙酮酸氧化产生适当的抑制。这些调查将有助于形成知识体系饮食建议最有利于维持体重可以配制较低水平的肥胖。