Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, USA.
Semin Reprod Med. 2011 May;29(3):237-45. doi: 10.1055/s-0031-1275517. Epub 2011 Jun 27.
A newly recognized primary cause of obesity epidemic is the developmental programming effects of (1) intrauterine growth-restricted (IUGR) newborns exposed in utero to undernutrition, and (2) normal or excessive weight newborns exposed to maternal obesity and high-fat (HF) diets. The mechanisms contributing to offspring obesity have been extensively studied in animal models with adipose tissue identified as one of the principal targets of programming. IUGR and HF offspring exhibit programmed adipocytes, such that an intrinsic enhanced lipogenesis and adipocyte proliferation contribute to the development of obesity. This is attributed to early induction of adipogenic transcription factor peroxisome proliferator-activated receptor (PPAR)γ, whose activity is enhanced under limited or excess nutrient availability. Nonetheless, this occurs via different mechanisms involving PPARγ coregulators: In IUGR, it is upregulation of coactivators, whereas in HF newborns, it is downregulation of corepressors. Thus preventive therapeutic interventions will require target-specific modalities that depend on the primary etiology.
一种新发现的肥胖症主要成因是（1）宫内生长受限（IUGR）新生儿在子宫内暴露于营养不良，以及（2）正常或超重新生儿暴露于母体肥胖和高脂肪（HF）饮食。在动物模型中，已经广泛研究了导致后代肥胖的机制，脂肪组织被确定为编程的主要靶标之一。IUGR 和 HF 后代表现出编程的脂肪细胞，使得内在增强的脂肪生成和脂肪细胞增殖有助于肥胖的发展。这归因于脂肪生成转录因子过氧化物酶体增殖物激活受体（PPAR）γ的早期诱导，其活性在有限或过量营养物质供应下增强。尽管如此，这是通过涉及 PPARγ 共激活因子的不同机制发生的：在 IUGR 中，是共激活因子的上调，而在 HF 新生儿中，是共抑制因子的下调。因此，预防性治疗干预将需要依赖于主要病因的特定于靶标的方式。
