Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA.
J Nutr. 2010 Mar;140(3):658-61. doi: 10.3945/jn.109.110155. Epub 2010 Jan 27.
Altered nutritional experiences such as undernutrition, overnutrition, and modified milk formula in the immediate postnatal life via the phenomenon of metabolic programming have been identified as one of the components in the etiology of metabolic syndrome. We have developed a rat model in which an altered dietary experience in the form of a high-carbohydrate (HC) milk formula in the immediate postnatal life of rat pups results in chronic hyperinsulinemia and adult-onset obesity in these rats. The HC dietary modification causes functional alterations in pancreatic islets and the hypothalamus during the period of the dietary modification. These early adaptations in islets (supporting hyperinsulinemia) and the hypothalamus (supporting hyperphagia and increased body weight gain) persist in the postweaning period despite withdrawal of the HC milk formula at the time of weaning. In female rat pups receiving the HC milk formula, metabolic programming effects translate into an adverse (hyperinsulinemic, hyperleptinemic, and obese) intrauterine environment during pregnancy, causing spontaneous transfer of the maternal phenotype to the progeny (generational effect). Our results suggest that alterations in feeding practices for babies (early introduction of cereals, fruits, etc.) and babies born to obese/hyperinsulinemic mothers may be contributing factors for the obesity epidemic prevalent in developed and developing countries.
改变营养体验，如生命早期的营养不良、营养过剩和配方奶改变，通过代谢编程现象，已被确定为代谢综合征病因学的组成部分之一。我们已经建立了一种大鼠模型，在该模型中，生命早期的高碳水化合物（HC）配方奶改变饮食，会导致这些大鼠出现慢性高胰岛素血症和成年肥胖。HC 饮食改变会导致胰岛和下丘脑在饮食改变期间发生功能改变。尽管在断奶时停止摄入 HC 配方奶，但这些早期的胰岛（支持高胰岛素血症）和下丘脑（支持多食和体重增加）适应会持续到断奶后。在接受 HC 配方奶的雌性幼鼠中，代谢编程效应转化为妊娠期间不利的（高胰岛素血症、高瘦素血症和肥胖）宫内环境，导致母系表型自发传递给后代（代际效应）。我们的研究结果表明，改变婴儿的喂养方式（早期引入谷物、水果等）以及肥胖/高胰岛素血症母亲所生婴儿可能是发达国家和发展中国家普遍存在肥胖流行的一个因素。
