Obese Pigs Fed a High Cholesterol Diet from Birth to 2 Months Are Less Susceptible than Lean Pigs to Atherosclerosis

Dietary cholesterol in infancy may alter cholesterol metabolism and the propensity to develop atherosclerosis. This study examined the effects of a 1% cholesterol diet (HC) vs. a no-cholesterol diet (NC) during the first 2 mo of life on pigs selectively bred for leanness or obesity. Three lean and three obese pigs received the no-cholesterol diet, and four lean and four obese pigs received the 1% cholesterol diet from d 1. Lean and obese pigs fed the no-cholesterol diet showed no increase in serum lipid concentrations, nor did they develop atherosclerosis. Obese pigs fed the 1% cholesterol diet developed significantly higher serum total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) at 35 d than lean pigs fed the 1% cholesterol diet. By d 55, only HDL-C remained significantly higher in the obese pigs, resulting in a higher (P < 0.1) TC/HDL-C ratio in the lean pigs. Atherosclerotic plaque formation in the aorta was more extensive in the lean pigs. Cholesterol synthesis measured in vivo and at termination was equally suppressed in lean and obese pigs fed the 1% cholesterol compared with pigs fed the no-cholesterol diet. We conclude that genetic differences in the response of these lean and obese pigs to a high cholesterol diet render obese pigs less susceptible to atherosclerosis despite higher serum TC concentrations. The persistent elevation of HDL-C in obese pigs is the most likely mechanism of protection.