Obesity, or an excess accumulation of body fat, usually accompanies aging. Obese individuals are at risk for many chronic diseases, such as hypertension, hyperlipidemia, diabetes and cardiovascular disease. There is evidence that many adverse effects of aging-related obesity are associated with the accretion of abdominal visceral fat over and beyond excess fat accumulated overall or in other anatomical regions. Moderate to severe reductions of caloric intake (i.e., 30-50% below ad libitum levels) produce decreased body fat, improvements in morbidity and mortality and increased longevity in many non-human species. The mechanisms underlying the benefits of caloric restriction are incompletely understood. We hypothesize that less sever caloric restrictions (i.e., 5-10-20% below ad libitum levels), like those that could reasonably be achieved by obese humans, can produce measurable benefits and that there are region-specific effects of caloric restriction on body fat. The goal of the proposed research is to develop an experimental animal model of mild to moderate chronic caloric restriction, using both genders of Wistar rates that exhibit spontaneous obesity with aging, to determine the effects of this type of food restriction on age-related growth, organ weight, and regional fat depot growth, cellularity (fat cell size and number), and fat cell metabolism (glucose conversion to CO2, triglycerides, lactate and pyruvate, response to insulin; and basal lipolysis, lipolytic response to norepinephrine). A unique feature of this proposal is a chronic food restriction paradigm that uses an automated feeder system capable of dispensing food at precise and graded levels, and indiscrete meals that mimic the natural nocturnal eating patter of rodents. Thus, the confounding effects of prolonged fasts and gorging behavior typical of most food restriction paradigms are avoided. The data generated by this short-term pilot study could then be used to design a more comprehensive study of the relationship of mild to moderate food restriction to body and organ growth, regional adiposity and fat cell metabolism, insulin sensitivity, Leptin and growth factors, and longevity, to be proposed in an RO1 application to the NIA.
| Porter, Marty H; Fine, Jacqueline B; Cutchins, Alexis G et al. (2004) Sexual dimorphism in the response of adipose mass and cellularity to graded caloric restriction. Obes Res 12:131-40 |
