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

Ninna S Hansen; Line Hjort; Christa Broholm; Linn Gillberg; Maren Schrölkamp; Heidi S Schultz; Brynjulf Mortensen; Sine W Jørgensen; Martin Friedrichsen; Jørgen F P Wojtaszewski; Bente K Pedersen; Allan Vaag

doi:10.1210/jc.2015-4214

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

Ninna S Hansen, Line Hjort, Christa Broholm, Linn Gillberg, Maren Schrölkamp, Heidi S Schultz, Brynjulf Mortensen, Sine W Jørgensen, Martin Friedrichsen, Jørgen F P Wojtaszewski, Bente K Pedersen, Allan Vaag

11 Citations (Scopus)

Abstract

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.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	101
Issue number	5
Pages (from-to)	2254-64
Number of pages	11
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2015-4214
Publication status	Published - May 2016

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Hansen, N. S., Hjort, L., Broholm, C., Gillberg, L., Schrölkamp, M., Schultz, H. S., Mortensen, B., Jørgensen, S. W., Friedrichsen, M., Wojtaszewski, J. F. P., Pedersen, B. K., & Vaag, A. (2016). Metabolic and Transcriptional Changes in Cultured Muscle Stem Cells from Low Birth Weight Subjects. The Journal of clinical endocrinology and metabolism, 101(5), 2254-64. https://doi.org/10.1210/jc.2015-4214

Hansen, NS, Hjort, L, Broholm, C, Gillberg, L, Schrölkamp, M, Schultz, HS, Mortensen, B, Jørgensen, SW, Friedrichsen, M, Wojtaszewski, JFP, Pedersen, BK & Vaag, A 2016, 'Metabolic and Transcriptional Changes in Cultured Muscle Stem Cells from Low Birth Weight Subjects', The Journal of clinical endocrinology and metabolism, vol. 101, no. 5, pp. 2254-64. https://doi.org/10.1210/jc.2015-4214

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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 F P

AU - Pedersen, Bente K

AU - Vaag, Allan

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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 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.

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 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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DO - 10.1210/jc.2015-4214

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JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 5

ER -

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

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