Obesity researchers are challenged to understand why the prevalence of obesity is increasing in the U.S. (NHANES III). In this application, we address this issue using an established model of dietary obesity in which some rats fed a high fat diet become obese while others do not. Our previous work has shown that both energy intake and energy efficiency are increased in those rats most susceptible to weight and fat gain. Enhanced energy efficiency implies that both energy expenditure and the relative contributions of nutrient storage and oxidation (nutrient partitioning) are involved in obesity susceptibility. Our preliminary results suggest that differences in energy intake explain approximately half of the variation in weight gain, leaving half to be explained by metabolic factors. Among the metabolic factors we have previously y identified as contributing to susceptibility to obesity include; 1) higher lipoprotein lipase activity in adipose tissue vs muscle; 2) greater capacity for carbohydrate vs fat utilization in skeletal and cardiac muscle; 3) reduced hepatic insulin action. We have further shown that metabolic differences are greatest after 1 week of high fat diet feeding.
The specific aims of this application are; 1) to understand, at tahe level of the whole body, how individual differences in energy intake, voluntary physical activity and substrate oxidation contribute to development of dietary obesity, 2) to understand how differences in nutrient partitioning at he enzymatic and tissue levels contribute to differences in whole body nutrient partitioning and obesity susceptibility, and 3) to understand the role of insulin action in dietary obesity.
These aims and the studies in this application are guided by a model of dietary obesity that has been developed during the past 4 years. According to the model, susceptibility to obesity is characterized by a slower ability to adjust the nutrient mixture oxidized to the nutrient mixture eaten. This slower adjustment is determined, in part, by the relateive capacities for tissue carbohydrate and fat utilization. Greater postprandial storage of nutrients is enhanced by the early induciton of hepatic insulin resistance, which forces more nutrient removal onto tissues like muscle and adipose tissue. In addition, athe extent and type (fat vs glycogen) of postprandial nutrient storage will be influenced by protein that regulate nutrient partitioning which are differentially affected by the high fat diet (nutrient-gene interaction). Our previous work suggests that the early events following access to the high fat diet determine the extent and type of acute nutrient storage. Whether and to what extent body fat accumulation will be maintained or increased will ultimately depend on whether or not there are compensatory changes in energy intake and/or energy expenditure.
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