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Am J Physiol Endocrinol Metab 296: E917-E924, 2009. First published January 27, 2009; doi:10.1152/ajpendo.90924.2008
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Maternal obesity downregulates myogenesis and β-catenin signaling in fetal skeletal muscle

Jun F. Tong,1 Xu Yan,1 Mei J. Zhu,1 Stephen P. Ford,1 Peter W. Nathanielsz,1,2 and Min Du1

1Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071; and 2Center for Pregnancy and Newborn Research, University of Texas Health Sciences Center, San Antonio, Texas 78229

Submitted 17 November 2008 ; accepted in final form 26 January 2009

Skeletal muscle is one of the primary tissues responsible for insulin resistance and type 2 diabetes (T2D). The fetal stage is crucial for skeletal muscle development. Obesity induces inflammatory responses, which might regulate myogenesis through Wnt/β-catenin signaling. This study evaluated the effects of maternal obesity (>30% increase in body mass index) during pregnancy on myogenesis and the Wnt/β-catenin and IKK/NF-{kappa}B pathways in fetal skeletal muscle using an obese pregnant sheep model. Nonpregnant ewes were assigned to a control group (C; fed 100% of National Research Council recommendations; n = 5) or obesogenic (OB; fed 150% of National Research Council recommendations; n = 5) diet from 60 days before to 75 days after conception (term ~148 days) when fetal semitendenosus skeletal muscle was sampled for analyses. Myogenic markers including MyoD, myogenin, and desmin contents were reduced in OB compared with C fetal semitendenosus, indicating the downregulation of myogenesis. The diameter of primary muscle fibers was smaller in OB fetal muscle. Phosphorylation of GSK3β was reduced in OB compared with C fetal semitendenosus. Although the β-catenin level was lower in OB than C fetal muscle, more β-catenin was associated with FOXO3a in the OB fetuses. Moreover, we found phosphorylation levels of IKKβ and RelA/p65 were both increased in OB fetal muscle. In conclusion, our data showed that myogenesis and the Wnt/β-catenin signaling pathway were downregulated, which might be due to the upregulation of inflammatory IKK/NF-{kappa}B signaling pathways in fetal muscle of obese mothers.

nuclear factor-{kappa}B; obesity; skeletal muscle; FOXO; inflammation



Address for reprint requests and other correspondence: M. Du, Dept. of Animal Science, Univ. of Wyoming, Laramie, WY 82071 (e-mail: mindu{at}uwyo.edu)




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