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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.

当获得食物不受限制时，必须氧化的限制一种代谢燃料组合，所含脂肪与饮食中的脂肪一样多，在确定身体脂肪方面的重要作用比整体能量消耗更重要。拟议中的调查的主要目标是测试其影响对这一概念的认识有助于理解富裕社会中的肥胖问题。使用独特的方法建立每日以及连续许多天累积的碳水化合物和脂肪平衡，它结合了24小时呼吸气体交换，食物摄入量和自发跑步活动测量，我们已经证明了重量随意喂养的小鼠的维持性是由食物的调节引起的摄入量，这主要是为了维持碳水化合物的需要而不是能量平衡。我们现在提议确定这是否是在遗传性肥胖的小鼠中也是如此，饮食脂肪是否也以剂量依赖的方式增加它们的体内脂肪含量。若要比较低脂饮食对高脂诱导肥胖的逆转作用饮食，他们引起的身体脂肪含量的变化将被跟踪用一种新的体积描记法测量活体密度动物。接下来，我们打算研究已知的变量是否会影响身体脂肪内容，如怀孕、锻炼、糖皮质激素或其拮抗剂、药物和寒冷暴露，通过它们对RQ的影响来实现和碳水化合物经济，从而对食物摄入量，以及对在多大程度上，这些影响可能会受到饮食中脂肪含量的影响。在……里面具体地说，我们将检验这样的假设，即脂肪在怀孕的部分原因是食物摄入量的增加以补偿胎儿氧化增加的葡萄糖，而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，胰岛素和胰岛素的相反作用游离脂肪酸浓度对丙酮酸氧化可能起到关键作用。在限制或促进肥胖的发展方面，通常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，氧化不会发生。来看看丙酮酸氧化的调节是如何在活体内，提供给正常和遗传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。评估碳水化合物的每日RQ模式的比较喂养期后的消散和糖原水平的测量以及通过化学身体分析得出的身体脂肪含量将被用于检查遗传性肥胖动物的身体成分有何不同适当抑制丙酮酸氧化。这些调查将有助于了解最易影响体重维持的饮食建议在较低水平的肥胖症是可以制定的。