HYPERCHOLESTEROLEMIA: SELECTIVE GENDER EFFECTS MINA DESAI, DAVE GAYLE, LINDA DAY, STACY BEHARE, MICHAEL ROSS, Harbor-UCLA Med. Ctr. (LA BioMed), Dept. of Ob/Gyn, Torrance, California OBJECTIVE: Maternal nutrient restriction results in IUGR offspring which develop programmed obesity. We determined the effect of high fat, Western diets on the sequalae of gestational programming, by examining the effects of a cafeteria diet (high fat, high calorie) on male and female lipid profile following maternal nutrient restriction. STUDY DESIGN: From day 10 to term gestation and through day 21 of lactation, Control pregnant rats received ad libitum (AdLib; n=6) food, whereas study dams were 50% food-restricted (FR) during pregnancy (FR/ AdLib; n=6) or lactation (AdLib/FR; n=6). Each litter size was culled to 4 males and 4 females. At age 3 weeks of age, one half of males and females from each of the maternal feeding groups were weaned to normal laboratory chow (9% fat calorie) and the remaining males and females were weaned to cafeteria diet (16% fat calorie). At 9 months of age, fasting plasma lipids were determined in offspring of each group (n=72). RESULTS: Plasma triglycerides, though not cholesterol, were markedly increased in FR/AdLib male (97G8 vs. 52G6 mg/dl, p!0.01) and female offspring (63G6 vs. 39G6 mg/dl, p!0.01) fed laboratory chow as compared to Controls. Cafeteria diet further increased triglycerides among both male and females of all maternal feeding groups. Cafeteria diet significant increased female cholesterol levels by 23% among FR/AdLib (86G6 to 106G9 mg/dl) and AdLib/FR offspring (90G8 to 110G9 mg/dl), though there was no effect in Control offspring (86G4 to 87G8 mg/dl). There was no effect of either of the maternal feeding paradigms or the cafeteria diet on male plasma cholesterol levels. CONCLUSION: Female, though not male, offspring exhibited programmed plasma hypercholesterolemia when challenged with postnatal cafeteria diet. The varying effects of maternal nutrient paradigms and cafeteria diets among males and females indicate differing pathophysiologic mechanisms which likely require gender-specific therapeutic approaches.