Desai Mina, Babu Jooby, Ross Michael G
Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles 90502, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Dec;293(6):R2306-14. doi: 10.1152/ajpregu.00783.2006. Epub 2007 Sep 26.
Maternal nutrient restriction results in intrauterine growth restriction (IUGR) newborns that develop obesity despite normal postweaning diet. The epidemic of metabolic syndrome is attributed to programmed "thrifty phenotype" and exposure to Western diets. We hypothesized that programmed IUGR newborns would demonstrate greater susceptibility to obesity and metabolic abnormalities in response to high-fat diet. From day 10 to term gestation and lactation, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% food restricted (FR). Cross-fostering techniques resulted in three offspring groups: control (AdLib/AdLib), FR during pregnancy (FR/AdLib), and FR during lactation (AdLib/FR). At 3 weeks, offspring were weaned to laboratory chow or high-fat calorie diet (9% vs. 17% calorie as fat). Body composition, appetite hormones, and glucose and lipid profiles were determined in 9-mo-old male and female offspring. High-fat diet had no effect on body weight of AdLib/AdLib, but significantly increased weights of FR/AdLib and AdLib/FR offspring. High-fat diet significantly increased body fat, reduced lean body mass, and accentuated plasma leptin but not ghrelin levels in both sexes in all groups. In males, high-fat diet caused a significant increase in glucose levels in all three groups with increased insulin levels in AdLib/AdLib and AdLib/FR, but not in FR/AdLib. In females, high-fat diet had no effect on glucose but significantly increased basal insulin among all three groups. High-fat diet caused hypertriglyceridemia in all three groups although only food-restricted females exhibited hypercholesterolemia. Sex and offspring phenotype-associated effects of high-fat diet indicate differing pathophysiologic mechanisms that require specific therapeutic approaches.
母体营养限制会导致宫内生长受限（IUGR）新生儿，这些新生儿尽管断奶后饮食正常，但仍会出现肥胖。代谢综合征的流行归因于程序化的“节俭表型”以及对西方饮食的接触。我们假设，程序化的IUGR新生儿对高脂饮食会表现出更高的肥胖易感性和代谢异常。从妊娠第10天到足月妊娠及哺乳期，对照孕鼠自由采食（AdLib）食物，而研究组孕鼠食物摄入量限制为50%（FR）。交叉寄养技术产生了三个后代组：对照组（AdLib/AdLib）、孕期FR组（FR/AdLib）和哺乳期FR组（AdLib/FR）。3周时，后代断奶并喂食实验室普通饲料或高脂高热量饮食（脂肪热量分别为9%和17%）。测定了9月龄雄性和雌性后代的身体组成、食欲激素以及血糖和血脂谱。高脂饮食对AdLib/AdLib组后代的体重没有影响，但显著增加了FR/AdLib组和AdLib/FR组后代的体重。高脂饮食显著增加了所有组两性的体脂，减少了瘦体重，并使血浆瘦素水平升高，但胃饥饿素水平未升高。在雄性中，高脂饮食导致所有三组的血糖水平显著升高，AdLib/AdLib组和AdLib/FR组的胰岛素水平升高，但FR/AdLib组未升高。在雌性中，高脂饮食对血糖没有影响，但显著增加了所有三组的基础胰岛素水平。高脂饮食在所有三组中均导致高甘油三酯血症，尽管只有食物受限的雌性表现出高胆固醇血症。高脂饮食的性别和后代表型相关效应表明存在不同的病理生理机制，需要采取特定的治疗方法。
