Toxicological Sciences, Vol 52, 49-55, Copyright © 1999 by Society of Toxicology
W Cefalu, J Wagner, A Bell-Farrow, I Edwards, J Terry, and
Caloric restriction (CR) has been observed to retard aging processes and
extend the maximum life span in rodents. In an effort to evaluate the
effect of this nutritional intervention on physiologic variables in higher
species, several nonhuman primate trials are ongoing. In particular, a
study evaluating the independent effect of CR on the extent of
atherosclerosis was initiated in 1993 in 32 adult cynomolgus monkeys.
Therefore, the trial was designed to achieve identical cholesterol intake
after animals were randomized to a control group or a calorie-restricted
group (30% reduction from baseline caloric intake). The animals were
routinely evaluated for glycated proteins, plasma insulin and glucose
levels, insulin sensitivity, and specific measures for abdominal fat
distribution by CT scans over a 4-year interval. The results from 4 years
of intervention demonstrate that CR improves cardiovascular risk factors
(such as visceral fat accumulation) and improves insulin sensitivity. In
contrast to other primate studies with normolipidemic animals, CR had no
independent effects on plasma lipid levels and composition in the presence
of equivalent amounts of dietary cholesterol intake. Preliminary analysis
of atherosclerotic lesion extent in the abdominal aorta has failed to
demonstrate differences between control animals and CR animals. Follow-up
studies are being conducted to determine the effect of CR on
atherosclerosis extent in coronary and carotid arteries.Keywords:
atherosclerosis; insulin; glucose; obesity; lipids
ARTICLES
Influence of caloric restriction on the development of atherosclerosis in nonhuman primates: progress to date
Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont, USA; Department of Medicine and Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Department of Medicine, University of Wisconsin-Madison, Madison, WI, USA; Wisconsin Regional Primate Center, Madison, WI, USA; GRECC, William S. Middleton VA Medical Center, Madison, WI, USA; Corresponding author address: Endocrine Unit, Given C331, University of Vermont College of Medicine, Burlington, VT 05405, USA; Fax: (802) 656-8031; E-mail: wcefalu@zoo.uvm.edu
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