Metabolic and Transcriptional Changes in Cultured Muscle Stem Cells from Low Birth Weight Subjects
| Autor: | Jørgen F. P. Wojtaszewski, Ninna S. Hansen, Heidi S. Schultz, Brynjulf Mortensen, Allan Vaag, Maren Schrölkamp, Sine W. Jørgensen, Martin Friedrichsen, Linn Gillberg, Bente Klarlund Pedersen, Christa Broholm, Line Hjort |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Birth weight Glucose uptake Muscle Fibers Skeletal Clinical Biochemistry 030209 endocrinology & metabolism Type 2 diabetes Biology Biochemistry Quadriceps Muscle Young Adult 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine Humans Cells Cultured Glucose Transporter Type 1 Myosin Heavy Chains Myogenesis Stem Cells Insulin Biochemistry (medical) Glucose transporter Infant Low Birth Weight medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha 030104 developmental biology Myogenin Stem cell Proto-Oncogene Proteins c-akt |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 101:2254-2264 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2015-4214 |
| Popis: | 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.We studied glucose uptake, glucose transporters, insulin signaling, key transcriptional markers of myotube maturity, selected site-specific DNA methylation, and mitochondrial gene expression.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.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. |
| Databáze: | OpenAIRE |
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