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

Mina Desai, PhD

Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California, Los Angeles, and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, mdesai@obgyn .humc.edu

Guang Han, MD

Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California, Los Angeles, and Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California

Monica Ferelli, PhD

Department of Urology, Harbor-UCLA Medical Center, Torrance, California

Natash Kallichanda, MD

Deparment of Pathology, Harbor-UCLA Medical Center, Torrance, California

Robert H. Lane, MD

Department of Pediatrics, University of Utah, Salt Lake City, Utah

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 (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 adipocytes. Paradoxical upregulation of adipogenesis signaling cascade prior to the development of obesity in IUGR males suggests early changes in signaling mechanisms.

Key Words: Adipocyte differentiation • peroxisome proliferator-activated receptor {gamma} • CCAAT enhancer-binding proteins • sterol regulatory element receptor y • CCAAT enhancer-binding proteins • sterol regulatory element binding protein • lipid enzymes.

Reproductive Sciences, Vol. 15, No. 8, 785-796 (2008)
DOI: 10.1177/1933719108318597
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