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

Jun F. Tong, Xu Yan, Mei J. Zhu, Stephen P. Ford, Peter W. Nathanielsz, Min Du

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

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-βB signaling pathways in fetal muscle of obese mothers.

Original languageEnglish (US)
Pages (from-to)E917-E924
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume296
Issue number4
DOIs
StatePublished - Apr 2009

Keywords

  • FOXO
  • Inflammation
  • Nuclear factor-κB
  • Obesity
  • Skeletal muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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