Sarr Ousseynou, Yang Kaiping, Regnault Timothy R H
Department of Obstetrics and Gynaecology, Children's Health Research Institute and Lawson Research Institute, University of Western Ontario, 1151 Richmond Street, London, ON, Canada N6A 5C1.
J Pregnancy. 2012;2012:134758. doi: 10.1155/2012/134758. Epub 2012 Nov 1.
Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity of the adipose master transcription factor regulator, peroxisome proliferator-activated receptor-γ (PPARγ) and its coregulators, increased lipogenic fatty acid synthase (FAS) expression and activity, and upregulation of glycolysis in fetal adipose tissue. Increased expression of fetal hypothalamic neuropeptide Y (NPY), altered hypothalamic leptin receptor expression and partitioning, reduced adipose noradrenergic sympathetic innervations, enhanced adipose glucocorticoid action, and modifications in methylation status in the promoter of hepatic and adipose adipogenic and lipogenic genes in the fetus also contribute to obesity following IUGR. Therefore, interventions that inhibit these fetal developmental changes will be beneficial for modulation of adult body fat accumulation.
宫内生长受限（IUGR）与成年后的肥胖密切相关。在动物模型和人类中，已经对导致IUGR相关成年肥胖症发病的机制进行了研究，其中胎儿脂肪组织发育、激素水平和表观基因组的变化已被确定为导致晚年肥胖的主要改变领域。在子宫内发育不良后，IUGR胎儿的脂肪细胞中脂肪生成和成脂能力增加、瘦素血症、糖皮质激素信号改变和染色质重塑，这些随后都导致晚年肥胖风险增加。数据表明，这些变化中的许多是由于脂肪主转录因子调节因子过氧化物酶体增殖物激活受体γ（PPARγ）及其共调节因子的活性增强、脂肪生成脂肪酸合酶（FAS）表达和活性增加以及胎儿脂肪组织中糖酵解上调所致。胎儿下丘脑神经肽Y（NPY）表达增加、下丘脑瘦素受体表达和分配改变、脂肪去甲肾上腺素能交感神经支配减少、脂肪糖皮质激素作用增强以及胎儿肝脏和脂肪中脂肪生成和脂肪生成基因启动子甲基化状态的改变也导致IUGR后的肥胖。因此，抑制这些胎儿发育变化的干预措施将有助于调节成年后的体脂积累。
