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Obese Pigs Fed a High Cholesterol Diet from Birth to 2 Months Are Less Susceptible than Lean Pigs to Atherosclerosis^1,2,3,

Anne M. Hackman, Wilson G. Pond^*,4, Harry J. Mersmann^*, William W. Wong, Lennart P. Krook^** and Shide Zhang

^* U.S. Department of Agriculture/Agricultural Research Services Children's Nutrition Research Center Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030 ^** Department of Pathology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853

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.

KEY WORDS: • cholesterol • atherosclerosis • infant • obesity • pigs

¹ This work is a publication of the U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX. This project has been funded in part with federal funds from the U.S. Department of Agriculture, Agricultural Research Service under Cooperative Agreement no. 58-6250-1-003. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.

² Presented in part by the senior author at the annual meeting of the American College of Cardiology, March 1994, Atlanta, GA [Hackman, A. M., Pond, W. G., Mersmann, H. J., Wong, W. W. & Krook, L. P. (1994). Hypercholesterolemia and atherosclerosis despite suppression of HMG-CoA reductase in lean and obese pigs fed high cholesterol from birth to two months. J. Am. Coll. Cardiol. 22: 99A (abs.)].

³ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

⁴ To whom correspondence should be addressed.

Manuscript received 15 May 1995. Revision accepted 31 October 1995.