Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609

Louise Groth Grunnet; Charlotte Brøns; Stine Jacobsen; Emma Nilsson; Arne Astrup; Torben Hansen; Oluf Pedersen; Pernille Poulsen; Bjørn Quistorff; Allan Vaag

doi:10.1210/jc.2008-1592

Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609

Louise Groth Grunnet, Charlotte Brøns, Stine Jacobsen, Emma Nilsson, Arne Astrup, Torben Hansen, Oluf Pedersen, Pernille Poulsen, Bjørn Quistorff, Allan Vaag

26 Citations (Scopus)

Abstract

Objective. Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated gene) to be associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Methods. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an intravenous glucose tolerance test, (31)phosphorous magnetic resonance spectroscopy and 24-hour whole body metabolism was measured in a respiratory chamber. Results. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance and shorter recovery halftimes of phosphocreatine (PCr) and inorganic phosphate (Pi) after exercise in a primarily type I muscle. These relationships - except for fasting insulin - remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-hour energy expenditure or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Conclusion. Increased energy efficiency - and potentially increased mitochondrial coupling - as suggested by faster recovery rates of PCr and Pi in oxidative muscle fibres may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk-allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated to the FTO phenotype.

Original language	English
Journal	Journal of Clinical Endocrinology and Metabolism
Volume	94
Issue number	2
Pages (from-to)	596-602
Number of pages	7
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2008-1592
Publication status	Published - 2009

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Grunnet, L. G., Brøns, C., Jacobsen, S., Nilsson, E., Astrup, A., Hansen, T., Pedersen, O., Poulsen, P., Quistorff, B., & Vaag, A. (2009). Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609. Journal of Clinical Endocrinology and Metabolism, 94(2), 596-602. https://doi.org/10.1210/jc.2008-1592

Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609. / Grunnet, Louise Groth; Brøns, Charlotte; Jacobsen, Stine et al.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 2, 2009, p. 596-602.

Research output: Contribution to journal › Journal article › Research › peer-review

Grunnet, LG, Brøns, C, Jacobsen, S, Nilsson, E, Astrup, A, Hansen, T, Pedersen, O, Poulsen, P, Quistorff, B & Vaag, A 2009, 'Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 2, pp. 596-602. https://doi.org/10.1210/jc.2008-1592

Grunnet LG, Brøns C, Jacobsen S, Nilsson E, Astrup A, Hansen T et al. Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609. Journal of Clinical Endocrinology and Metabolism. 2009;94(2):596-602. doi: 10.1210/jc.2008-1592

Grunnet, Louise Groth ; Brøns, Charlotte ; Jacobsen, Stine et al. / Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 2. pp. 596-602.

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title = "Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609",

abstract = "Objective. Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated gene) to be associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Methods. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an intravenous glucose tolerance test, (31)phosphorous magnetic resonance spectroscopy and 24-hour whole body metabolism was measured in a respiratory chamber. Results. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance and shorter recovery halftimes of phosphocreatine (PCr) and inorganic phosphate (Pi) after exercise in a primarily type I muscle. These relationships - except for fasting insulin - remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-hour energy expenditure or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Conclusion. Increased energy efficiency - and potentially increased mitochondrial coupling - as suggested by faster recovery rates of PCr and Pi in oxidative muscle fibres may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk-allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated to the FTO phenotype.",

author = "Grunnet, {Louise Groth} and Charlotte Br{\o}ns and Stine Jacobsen and Emma Nilsson and Arne Astrup and Torben Hansen and Oluf Pedersen and Pernille Poulsen and Bj{\o}rn Quistorff and Allan Vaag",

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doi = "10.1210/jc.2008-1592",

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T1 - Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibres and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609

AU - Grunnet, Louise Groth

AU - Brøns, Charlotte

AU - Jacobsen, Stine

AU - Nilsson, Emma

AU - Astrup, Arne

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Poulsen, Pernille

AU - Quistorff, Bjørn

AU - Vaag, Allan

PY - 2009

Y1 - 2009

N2 - Objective. Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated gene) to be associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Methods. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an intravenous glucose tolerance test, (31)phosphorous magnetic resonance spectroscopy and 24-hour whole body metabolism was measured in a respiratory chamber. Results. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance and shorter recovery halftimes of phosphocreatine (PCr) and inorganic phosphate (Pi) after exercise in a primarily type I muscle. These relationships - except for fasting insulin - remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-hour energy expenditure or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Conclusion. Increased energy efficiency - and potentially increased mitochondrial coupling - as suggested by faster recovery rates of PCr and Pi in oxidative muscle fibres may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk-allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated to the FTO phenotype.

AB - Objective. Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated gene) to be associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Methods. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an intravenous glucose tolerance test, (31)phosphorous magnetic resonance spectroscopy and 24-hour whole body metabolism was measured in a respiratory chamber. Results. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance and shorter recovery halftimes of phosphocreatine (PCr) and inorganic phosphate (Pi) after exercise in a primarily type I muscle. These relationships - except for fasting insulin - remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-hour energy expenditure or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Conclusion. Increased energy efficiency - and potentially increased mitochondrial coupling - as suggested by faster recovery rates of PCr and Pi in oxidative muscle fibres may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk-allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated to the FTO phenotype.

U2 - 10.1210/jc.2008-1592

DO - 10.1210/jc.2008-1592

M3 - Journal article

C2 - 18984658

SN - 0021-972X

VL - 94

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EP - 602

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

IS - 2

ER -