Metabolic and transcriptional changes in cultured muscle stem cells from low birth weight subjects

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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 risk of developing T2D. Design/settings/participants: We recruited 23 young men with LBW and 16 age-matched control subjects with normal birth weight (NBW). 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 NBW individuals. The myogenic differentiation markers, myogenin and myosin heavy chain 1 and 2, were decreased during late differentiation in LBW myotubes. Additionally, the mRNA level 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 towards a retained intrinsic defect conserved in these myotubes.

TidsskriftJournal of Clinical Endocrinology and Metabolism
Udgave nummer5
Sider (fra-til)2254-2264
Antal sider11
StatusUdgivet - 2016

Bibliografisk note

CURIS 2016 NEXS 099

ID: 160059131