Metabolic and transcriptional changes in cultured muscle stem cells from low birth weight subjects
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Metabolic and transcriptional changes in cultured muscle stem cells from low birth weight subjects. / Hansen, Ninna S; Hjort, Line; Broholm, Christa; Gillberg, Linn; Schrölkamp, Maren; Schultz, Heidi S; Mortensen, Brynjulf; Jørgensen, Sine W; Friedrichsen, Martin; Wojtaszewski, Jørgen; Pedersen, Bente Klarlund; Vaag, Allan.
I: Journal of Clinical Endocrinology and Metabolism, Bind 101, Nr. 5, 2016, s. 2254-2264.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Metabolic and transcriptional changes in cultured muscle stem cells from low birth weight subjects
AU - Hansen, Ninna S
AU - Hjort, Line
AU - Broholm, Christa
AU - Gillberg, Linn
AU - Schrölkamp, Maren
AU - Schultz, Heidi S
AU - Mortensen, Brynjulf
AU - Jørgensen, Sine W
AU - Friedrichsen, Martin
AU - Wojtaszewski, Jørgen
AU - Pedersen, Bente Klarlund
AU - Vaag, Allan
N1 - CURIS 2016 NEXS 099
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1210/jc.2015-4214
DO - 10.1210/jc.2015-4214
M3 - Journal article
C2 - 27003303
VL - 101
SP - 2254
EP - 2264
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 5
ER -
ID: 160059131