Maternal obesity downregulates myogenesis and β-catenin signaling in fetal skeletal muscle

JF Tong, X Yan, MJ Zhu, SP Ford… - American Journal …, 2009 - journals.physiology.org
JF Tong, X Yan, MJ Zhu, SP Ford, PW Nathanielsz, M Du
American Journal of Physiology-Endocrinology and Metabolism, 2009journals.physiology.org
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-κB pathways in fetal
skeletal muscle using an obese pregnant sheep model. Nonpregnant ewes were assigned …
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-κB 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-κB signaling pathways in fetal muscle of obese mothers.
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