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Abstract

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. Oneday-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.

Keywords

Adipocyte differentiation peroxisome proliferator-activated receptor γ CCAAT enhancer-binding proteins sterol regulatory element receptor y sterol regulatory element binding protein lipid enzymes.

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

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