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

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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 (PPARγ2), 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.

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Author information

Authors and Affiliations

  1. Perinatal Research Laboratories, Department of Obstetrics and Gynecology, David-Geffen School of Medicine at University of California, Los Angeles, USA

    Mina Desai PhD & Guang Han MD

  2. Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Box 446, RB-1 Bldg, Torrance, California, 90502, USA

    Mina Desai PhD & Guang Han MD

  3. Department of Urology, Harbor-UCLA Medical Center, Torrance, California, USA

    Monica Ferelli PhD

  4. Department of Pathology, Harbor-UCLA Medical Center, Torrance, California, USA

    Natash Kallichanda MD

  5. Department of Pediatrics, University of Utah, Salt Lake City, Utah, USA

    Robert H. Lane MD

Authors
  1. Mina Desai PhD
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  2. Guang Han MD
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  3. Monica Ferelli PhD
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  4. Natash Kallichanda MD
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  5. Robert H. Lane MD
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Corresponding author

Correspondence to Mina Desai PhD.

Additional information

This work was supported by the National Institutes of Health K01 DK 063994 and the March of Dimes.

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Desai, M., Han, G., Ferelli, M. et al. Programmed Upregulation of Adipogenic Transcription Factors in Intrauterine Growth-Restricted Offspring. Reprod. Sci. 15, 785–796 (2008). https://doi.org/10.1177/1933719108318597

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