Programmed Upregulation of Adipogenic Transcription Factors in Intrauterine Growth-Restricted Offspring

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, rates received ad libitum food (control) or were 50% food-restricted (IUGR). Pups were nursed and weaned to ad libitum diet. mRNA and adipocyte cell size (3 weeks and 9 months) were determined. One-day-old IUGR males showed upregulation of peroxisome proliferator-activated receptor (PPAR gamma(2)), including upstream factors regulating PPAR gamma, and RXR alpha, with which PPAR gamma 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 adipoctyes. Paradoxical upregulation of adipogensis signaling cascade prior to the development of obesity in IUGR males suggests early changes in signaling mechanisms.