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

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

doi:10.1152/ajpendo.90924.2008

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

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

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

American journal of physiology: endocrinology and metabolism, Vol.296(4), pp.E917-924

04/2009

DOI: https://doi.org/10.1152/ajpendo.90924.2008

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https://hdl.handle.net/2376/104742

PMCID: PMC2670630

PMID: 19176350

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https://doi.org/10.1152/ajpendo.90924.2008View

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Abstract

Maternal Nutritional Physiological Phenomena

Fetus - metabolism

Muscle, Skeletal - metabolism

Wnt Proteins - metabolism

Fetus - physiology

Female

beta Catenin - physiology

Muscle, Skeletal - embryology

Fetus - anatomy & histology

Muscle, Skeletal - anatomy & histology

Pregnancy Complications - veterinary

Down-Regulation

Muscle Development - physiology

Obesity - physiopathology

Organ Size - physiology

Maternal-Fetal Exchange - physiology

Muscle, Skeletal - physiology

Pregnancy Complications - physiopathology

beta Catenin - metabolism

Obesity - metabolism

Pregnancy

Animals

Sheep

Signal Transduction - physiology

Obesity - veterinary

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-kappaB 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 approximately 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 GSK3beta 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 IKKbeta 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-kappaB signaling pathways in fetal muscle of obese mothers.

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Title: Maternal obesity downregulates myogenesis and beta-catenin signaling in fetal skeletal muscle
Creators: Jun F Tong - Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA
Xu Yan
Mei J Zhu
Stephen P Ford
Peter W Nathanielsz
Min Du
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.296(4), pp.E917-924
Academic Unit: Animal Sciences, Department of
Publisher: United States
Grant note: P01 HD021350 / NICHD NIH HHS 1R03HD-057506 / NICHD NIH HHS
Identifiers: 99900547084701842
Language: English
Resource Type: Journal article