Elevated plasma cholesterol concentration is a major risk factor for the development of atherosclerosis. Cholesterol metabolism changes with age. As suggested by recent evidence from studies in animals, response to the quality and quantity of dietary cholesterol and fat may be responsible for at least a proportion of the change in total plasma cholesterol concentration and cholesterol metabolism observed with aging in Western societies. Our hypothesis is that an individual's ability or inability to acclimate to cholesterol and saturated fat in their diet may influence the magnitude of the increase in TPC concentration observed with aging. The phenomenon of dietary acclimation is well documented in non-human primates. Dietary acclimation is a metabolic adaptation in which the rise in plasma cholesterol concentration induced by the introduction of dietary cholesterol and fat may be partially or completely reversed after a period of twelve or more months on such a diet. The proposed project, to clarify the mechanisms for acclimation to dietary cholesterol and fat in Macaca fascicularis, a model relevant to human lipoprotein metabolism, will lend potential insight into the differential responses to diet that may occur across the lifespan of human beings.
The research aims are to characterize the components of cholesterol metabolism responsible for the observed changes in plasma cholesterol concentration in animals that acclimate i.e. 1) production and catabolism of apoprotein B containing lipoproteins; 2) gastrointestinal absorption of cholesterol; 3) biliary excretion of cholesterol. In addition, the applicant will participate in the active geriatric medicine program at Bowman Gray School of Medicine which includes: In-hospital consultation team; geriatric outpatient assessment clinic; long-term nursing home care at the North Carolina Baptist Home for the Aged. Clinical teaching will involve precepting students, resident and fellows in the above settings. The applicant will prepare didactic talks for the weekly geriatric medicine conference and for the housestaff medicine conferences. The applicant will participate in the instruction of second year medical students during their required course in gerontology and geriatric medicine.
