Intrauterine Growth Restriction, Small for Gestational Age, and Experimental Obesity

  • Michael G. Ross
  • Ivan Huber
  • Mina Desai
Part of the Endocrine Updates book series (ENDO, volume 30)


Both high and low birth weight (LBW) have a programmed predisposition to adult metabolic syndrome, which is exacerbated by exposure to Western high-fat diets. This review discusses animal models of obesity, including programming during embryonic, fetal, and postnatal periods. Programming affects a diversity of organ systems, but we focus specifically on central appetite function and peripheral adipogenesis/lipogenesis. Appetite is regulated by hypothalamic orexigenic and anorexigenic pathways, the neurons of which receive central (e.g., synaptic) and peripheral (e.g., leptin, ghrelin, insulin) input which adjust orexigenic drive. In humans, appetite pathways are well developed while satiety circuits are notably less functional, contributing to the difficulty of self-motivated dietary weight loss. The analysis of neural stem cell cultures (NSCs) has provided an insight into how leptin and insulin deficiency, associated with LBW, may permanently affect development of hypothalamic appetite pathways and thus program ingestive behavior. In regards to programmed adiposity, we review the pivotal role of the adipogenic transcription factor PPARγ, which promotes both adipogenesis and lipogenesis, contributing to the development of obesity. Neonatal leptin supplementation may prevent programmed obesity in animal models of LBW. Although this hormone may be considered as an additive for LBW humans, additional studies are needed prior to clinical intervention. Further research is needed for approaches to the optimization of fetal growth throughout pregnancy. In the interim, maternal breastfeeding of LBW and normal weight newborns should be encouraged.


Hypothalamic programming Metabolic syndrome Appetite Satiety Adipogenesis Lipogenesis 


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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyHarbor-UCLA Medical CenterTorranceUSA
  2. 2.Department of Obstetrics and GynecologyDavid Geffen School of Medicine at Harbor-UCLA Medical SchoolTorranceUSA

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