Prenatal Low-Protein and Postnatal High-Fat Diets Induce Rapid Adipose Tissue Growth by Inducing Igf2 Expression in Sprague Dawley Rat Offspring
Prenatal Low-Protein and Postnatal High-Fat Diets Induce Rapid Adipose Tissue Growth by Inducing Igf2 Expression in Sprague Dawley Rat Offspring
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DOI：
10.3945/jn.113.178038
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发表时间：
2013-10-01
影响因子：
4.2
通讯作者：
Johnson, W. Thomas
中科院分区：
文献类型：
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作者：
Claycombe, Kate J.;Uthus, Eric O.;Johnson, W. Thomas
产妇低蛋白饮食会导致出生体重较低，随后会加速追赶生长，并伴随着晚年肥胖和葡萄糖耐受不良的发展。目前尚不清楚出生后高脂饮食是否通过影响脂肪组织代谢和DNA甲基化进一步导致后代肥胖和胰岛素抵抗的发展。在受孕前、整个妊娠期和哺乳期，向肥胖倾向的Sprague-Dawley大鼠喂食8%低蛋白（LP）或20%正常蛋白饮食3周，以研究产前LP和产后HF饮食是否影响雄性后代的脂肪组织生长速率、胰岛素样生长因子2（Igf 2）表达和DNA甲基化。断奶时，后代饲喂10%正常脂肪或45% HF饲料12周。脂肪组织生长率增加（高达26倍）的LP产前和HF产后饮食。脂肪组织Igf 2 mRNA和DNA甲基化增加LP产前和HF产后饮食。出生前LP和出生后HF饮食增加了脂肪组织中小脂肪细胞的数量，降低了胰岛素敏感性。这些发现表明，产前LP和出生后HF摄入导致脂肪组织追赶生长，通过改变Igf 2基因的表达和脂肪细胞内的DNA甲基化。肥胖的这些改变伴随着2型糖尿病发展的风险增加。
Maternal low-protein diets result in lower birth weight followed by accelerated catch-up growth that is accompanied by the development of obesity and glucose intolerance in later life. Whether postnatal high-fat (HF) diets further contribute to the development of obesity and insulin resistance in offspring by affecting adipose tissue metabolism and DNA methylation is currently unknown. Obese-prone Sprague-Dawley rats were fed 8% low protein (LP) or 20% normal protein diets for 3 wk prior to conception and throughout pregnancy and lactation to investigate whether prenatal LP and postnatal HF diets affect the rate of adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation in male offspring. At weaning, the offspring were fed 10% normal fat or 45% HF diets for 12 wk. The adipose tissue growth rate was increased (up to 26-fold) by the LP prenatal and HF postnatal diets. Adipose tissue Igf2 mRNAs and DNA methylation were increased by the LP prenatal and HF postnatal diets. The LP prenatal and HF postnatal diet increased the number of small adipocytes in adipose tissue and decreased insulin sensitivity. These findings suggest that prenatal LP and postnatal HF intake result in adipose tissue catch-up growth through alterations in the expression of the Igf2 gene and DNA methylation within adipocytes. These alterations in adiposity are accompanied by an increased risk of development of type 2 diabetes.