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

• Published in: The journal of clinical endocrinology and metabolism Vol. 101; no. 5; pp. 2254 - 2264
• Main Authors: Hansen, Ninna S., Hjort, Line, Broholm, Christa, Gillberg, Linn, Schrölkamp, Maren, Schultz, Heidi. S., Mortensen, Brynjulf, Jørgensen, Sine W., Friedrichsen, Martin, Wojtaszewski, Jørgen F. P., Pedersen, Bente K., Vaag, Allan
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2016; Copyright by The Endocrine Society
• Subjects: Adult; AKT protein; Biopsy; Birth weight; Cell differentiation; Cells, Cultured; Cytochrome-c oxidase; Diabetes mellitus (non-insulin dependent); DNA methylation; Gene expression; Glucose; Glucose transporter; Glucose Transporter Type 1 - genetics; Glucose Transporter Type 1 - metabolism; Humans; Infant, Low Birth Weight; Low birth weight; Male; Metabolism; Mitochondrial DNA; Muscle Fibers, Skeletal - cytology; Muscle Fibers, Skeletal - metabolism; Myogenin; Myogenin - genetics; Myogenin - metabolism; Myosin; Myosin Heavy Chains - genetics; Myosin Heavy Chains - metabolism; Myotubes; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Peroxisome proliferator-activated receptors; Protein transport; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Quadriceps Muscle - cytology; Quadriceps Muscle - metabolism; Satellite cells; Satellite DNA; Stem Cells; Transcription; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2015-4214

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.