Article open access publication

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

The Journal of Clinical Endocrinology & Metabolism, The Endocrine Society, ISSN 1945-7197

Volume 101, 5, 2016

DOI:10.1210/jc.2015-4214, Dimensions: pub.1008289530, PMID: 27003303,

Affiliations

Organisations

  1. (1) Novo Nordisk (Denmark), grid.425956.9
  2. (2) Rigshospitalet, grid.475435.4, Capital Region

Countries

Denmark

Continents

Europe

Description

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.

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University of Copenhagen

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Times Cited: 5

Field Citation Ratio (FCR): 2.43

Relative Citation ratio (RCR): 0.3

Open Access Info

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