title: Maternal obesity downregulates myogenesis and beta-catenin signaling in fetal skeletal muscle.
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/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.
authors.affiliation: Center for the Study of Fetal Programming, Department of Animal Science, University of Wyoming, Laramie, WY 82071, USA.
authors.forename: Jun F
authors.initials: JF
authors.lastname: Tong
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.forename: Mei J
authors.initials: MJ
authors.lastname: Zhu
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Ford
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005260:Female; D005333:Fetus / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology; D039382:Maternal Nutritional Physiological Phenomena; D008431:Maternal-Fetal Exchange / Q000502:physiology; D024510:Muscle Development / Q000502:physiology*; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism / Q000502:physiology*; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology* / Q000662:veterinary; D009929:Organ Size / Q000502:physiology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology* / Q000662:veterinary; D012756:Sheep; D015398:Signal Transduction / Q000502:physiology; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism* / Q000502:physiology
chemical_list: D051153:Wnt Proteins; D051176:beta Catenin