Journal
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
Volume 296, Issue 4, Pages E917-E924Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.90924.2008
Keywords
nuclear factor-kappa B; obesity; skeletal muscle; FOXO; inflammation
Categories
Funding
- U.S. Department of Agriculture-Cooperative State Research, Education, and Extension Service [2007-35203-18065, 2006-55618-16914]
- National Institute of Child Health and Human Development [1R03HD-057506]
- Division of Research Resources (IDeA Network of Biomedical Research Excellence) [P20 RR-016474-04]
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Tong JF, Yan X, Zhu MJ, Ford SP, Nathanielsz PW, Du M. Maternal obesity downregulates myogenesis and beta-catenin signaling in fetal skeletal muscle. Am J Physiol Endocrinol Metab 296: E917-E924, 2009. First published January 27, 2009; doi:10.1152/ajpendo.90924.2008.-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/beta-catenin signaling. This study evaluated the effects of maternal obesity (>30% increase in body mass index) during pregnancy on myogenesis and the Wnt/beta-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 similar to 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 GSK3 beta was reduced in OB compared with C fetal semitendenosus. Although the beta-catenin level was lower in OB than C fetal muscle, more beta-catenin was associated with FOXO3a in the OB fetuses. Moreover, we found phosphorylation levels of IKK beta and RelA/p65 were both increased in OB fetal muscle. In conclusion, our data showed that myogenesis and the Wnt/beta-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.
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