As enhanced adipogenesis contributes to programmed obesity, adipogenic and lipogenic signaling pathways in intrauterine growth restricted (IUGR) offspring were examined. From 10 days to term gestation, rats received ad libitum food (control) or were 50% food-restricted (IUGR). Pups were nursed and weaned to ad libitum diet. mRNA and protein levels of adipogenic transcription factors and lipid enzymes (1 day and 9 month) and adipocyte cell size (3 weeks and 9 months) were determined. One-day-old IUGR males showed upregulation of peroxisome proliferator-activated receptor (PPARγ 2 ), including upstream factors regulating PPARγ, and RXRα, with which PPARγ heterodimerizes. Intracellular lipolytic enzyme (hormone-sensitive lipase) was downregulated. Nine-month-old IUGR males showed upregulation of adipogenic and lipogenic (SREBP1c) transcription factors with upregulation of enzymes facilitating fatty acid uptake (lipoprotein lipase) and synthesis (fatty acid synthase), leading to hypertrophic adipocytes. Paradoxical upregulation of adipogenesis signaling cascade prior to the development of obesity in IUGR males suggests early changes in signaling mechanisms.
KeywordsAdipocyte differentiation; peroxisome proliferator-activated receptor γ; CCAAT enhancerbinding proteins; sterol regulatory element binding protein; lipid enzymes Obesity has emerged as a preeminent public health problem.1 , 2 Furthermore, obesity is a major risk factor for diabetes and atherosclerosis, afflictions associated with a constellation of insulin resistance, hypertension, and lipid abnormalities.3 One of the underlying factors that links these disorders is a dysregulation of white adipose tissue mass or enhanced adipogenesis,4 resulting in alterations in adipocyte size and/or number.5 , 6 Adipogenesis, in turn, is triggered by the induction of adipocyte differentiation, which leads to lipogenesis and hence lipid accumulation within the adipocyte.5 , 7Adipocyte differentiation is triggered by a set of interacting transcription factors.8 , 9 In particular, the peroxisome proliferator-activated receptor (PPAR) and CCAAT/enhancer binding protein (C/EBP) family members play a cooperative role in influencing adipocyte © 2008 Human and animal models have highlighted the critical role of early nutrition in influencing adiposity and lipid metabolism. Paradoxically, both maternal nutrition deprivation20 , 21 and maternal obesity22 produce obese offspring though the underlying mechanisms remain unclear. Intrauterine growth-restricted (IUGR) newborns have increased risk of obesity, especially when it is associated with catch-up growth in the first few years of life. To reflect this scenario, we have established a rat model of maternal food restriction during pregnancy that results in IUGR newborns. When provided standard nursing and postweaning diet, IUGR newborns demonstrate rapid catch-up growth hyperphagia and adult obesity. In particular, they develop obesity as adults, with excess body fat and increased plasma levels of leptin, insulin, gluco...
