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
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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; Nilsson, Emma; Astrup, Arne; Hansen, Torben; Pedersen, Oluf; Poulsen, Pernille; Quistorff, Bjørn; Vaag, Allan.
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
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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
VL - 94
SP - 596
EP - 602
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 2
ER -
ID: 10000856