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Title: Programming Body Composition in Offspring by Maternal Obesity Is Associated with Increased Adipogenesis and Decreased WNT/ Beta-Catenin Signaling in the Adipose Tissue

item Shankar, Kartik
item Harrell, Amanda
item Gilchrist, Janet
item Ronis, Martin
item Badger, Thomas

Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 1/31/2008
Publication Date: 4/7/2008
Citation: Shankar, K., Harrell, A., Gilchrist, J.M., Ronis, M.J., Badger, T.M. 2008. Programming body composition in offspring by maternal obesity is associated with increased adipogenesis and decreased WNT/ beta-catenin signaling in the adipose tissue [abstract]. The FASEB Journal. 22:2223.

Interpretive Summary:

Technical Abstract: Maternal obesity during pregnancy significantly influences the risk of obesity in the offspring. We recently demonstrated that maternal obesity at conception programs obesity in the offspring. Obese dam offspring when weaned on high-fat diets gain significantly greater body weight/adiposity (via NMR and CT) and insulin resistance than lean dam offspring on the same diet. Histomorphometry revealed greater adipose hypertrophy in offspring of obese dams. To examine the underlying mechanisms of obesity-induced programming, we examined wnt/and [beta]-catenin signaling, a critical negative regulator of adipogenesis. Analyses of 85 genes involved in Wnt/and [beta]-catenin signaling revealed significant induction of wnt signaling antagonists, Sfrp2, 4, dickkopf 1, and wif1 specifically in the adipose tissue of offspring of obese dams. Conversely, lean dam offspring showed significant reduction in Sfrp5. Consistent with these results, cellular phospho-GSK3 and [beta] and nuclear and [beta]-catenin levels in adipose tissue were significantly lower in offspring of obese rats compared to their lean counterparts. In addition, protein levels of adipogenic factors PPAR-and [gamma] and C/EBP-and [alpha] were significantly increased in offspring of obese dams. Our data suggest that maternal obesity at conception leads to programming of the Wnt/and [beta]-catenin pathway in the offspring, which may contribute to greater adipogenesis and obesity later in life.