Metabolic and Transcriptional Changes in Cultured Muscle Stem Cells from Low Birth Weight Subjects

Ninna S Hansen, Line Hjort, Christa Broholm, Linn Gillberg, Maren Schrölkamp, Heidi S Schultz, Brynjulf Mortensen, Sine W Jørgensen, Martin Friedrichsen, Jørgen F P Wojtaszewski, Bente K Pedersen, Allan Vaag

    11 Citations (Scopus)


    CONTEXT/OBJECTIVE: Developmental programming of human muscle stem cells could in part explain why individuals born with low birth weight (LBW) have an increased risk of developing type 2 diabetes (T2D) later in life. We hypothesized that immature muscle stem cell functions including abnormal differentiation potential and metabolic function could link LBW with the risk of developing T2D. Design/Settings/Participants: We recruited 23 young men with LBW and 16 age-matched control subjects with normal birth weight. Biopsies were obtained from vastus lateralis, and muscle stem cells were isolated and cultured into fully differentiated myotubes.

    MAIN OUTCOME MEASURES: We studied glucose uptake, glucose transporters, insulin signaling, key transcriptional markers of myotube maturity, selected site-specific DNA methylation, and mitochondrial gene expression.

    RESULTS: We found reduced glucose uptake as well as decreased levels of glucose transporter-1 and -4 mRNA and of the Akt substrate of 160-kDa mRNA and protein in myotubes from LBW individuals compared with normal birth weight individuals. The myogenic differentiation markers, myogenin and myosin heavy chain 1 and 2, were decreased during late differentiation in LBW myotubes. Additionally, mRNA levels of the peroxisome proliferator-activated receptor-γ coactivator-1α and cytochrome c oxidase polypeptide 7A were reduced in LBW myotubes. Decreased gene expression was not explained by changes in DNA methylation levels.

    CONCLUSION: We demonstrate transcriptional and metabolic alterations in cultured primary satellite cells isolated from LBW individuals after several cell divisions, pointing toward a retained intrinsic defect conserved in these myotubes.

    Original languageEnglish
    JournalThe Journal of clinical endocrinology and metabolism
    Issue number5
    Pages (from-to)2254-64
    Number of pages11
    Publication statusPublished - May 2016


    • Journal Article


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