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Regulation and Function of FTO mRNA Expression in Human Skeletal Muscle and Subcutaneous Adipose Tissue

Grunnet, Louise G.; Nilsson, Emma; Ling, Charlotte LU ; Hansen, Torben; Pedersen, Oluf; Groop, Leif LU ; Vaag, Allan and Poulsen, Pernille (2009) In Diabetes 58(10). p.2402-2408
Abstract
OBJECTIVE-Common variants in FTO (the fat mass- and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN AND METHODS-The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years) nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including indirect calorimetry. FTO mRNA expression was... (More)
OBJECTIVE-Common variants in FTO (the fat mass- and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN AND METHODS-The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years) nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n = 226) and skeletal muscle biopsies (n = 158). RESULTS-Heritability of FTO expression in both tissues was low, and FTO expression was not influenced by FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA expression. FTO mRNA expression in adipose tissue was associated with an atherogenic lipid profile. In skeletal muscle, FTO mRNA expression was negatively associated to fat and positively to glucose oxidation rates as well as positively correlated with expression of genes involved in oxidative phosphorylation including PGC1 alpha. CONCLUSIONS-The heritability of FTO expression in adipose tissue and skeletal muscle is low and not influenced by obesity-associated FTO genotype. The age-dependent decline in FTO expression is associated with peripheral defects of glucose and fat metabolism. Diabetes 58:2402-2408, 2009 (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
58
issue
10
pages
2402 - 2408
publisher
American Diabetes Association Inc.
external identifiers
  • wos:000270776200028
  • scopus:70349642879
ISSN
1939-327X
DOI
10.2337/db09-0205
language
English
LU publication?
yes
id
ee42e43b-d4b5-414e-ba9c-7b7a22fb19ab (old id 1506990)
date added to LUP
2009-11-23 10:34:57
date last changed
2017-05-14 03:56:31
@article{ee42e43b-d4b5-414e-ba9c-7b7a22fb19ab,
  abstract     = {OBJECTIVE-Common variants in FTO (the fat mass- and obesity-associated gene) associate with obesity and type 2 diabetes. The regulation and biological function of FTO mRNA expression in target tissue is unknown. We investigated the genetic and nongenetic regulation of FTO mRNA in skeletal muscle and adipose tissue and their influence on in vivo glucose and fat metabolism. RESEARCH DESIGN AND METHODS-The FTO rs9939609 polymorphism was genotyped in two twin cohorts: 1) 298 elderly twins aged 62-83 years with glucose tolerance ranging from normal to type 2 diabetes and 2) 196 young (25-32 years) and elderly (58-66 years) nondiabetic twins examined by a hyperinsulinemic-euglycemic clamp including indirect calorimetry. FTO mRNA expression was determined in subcutaneous adipose tissue (n = 226) and skeletal muscle biopsies (n = 158). RESULTS-Heritability of FTO expression in both tissues was low, and FTO expression was not influenced by FTO rs9939609 genotype. FTO mRNA expression in skeletal muscle was regulated by age and sex, whereas age and BMI were predictors of adipose tissue FTO mRNA expression. FTO mRNA expression in adipose tissue was associated with an atherogenic lipid profile. In skeletal muscle, FTO mRNA expression was negatively associated to fat and positively to glucose oxidation rates as well as positively correlated with expression of genes involved in oxidative phosphorylation including PGC1 alpha. CONCLUSIONS-The heritability of FTO expression in adipose tissue and skeletal muscle is low and not influenced by obesity-associated FTO genotype. The age-dependent decline in FTO expression is associated with peripheral defects of glucose and fat metabolism. Diabetes 58:2402-2408, 2009},
  author       = {Grunnet, Louise G. and Nilsson, Emma and Ling, Charlotte and Hansen, Torben and Pedersen, Oluf and Groop, Leif and Vaag, Allan and Poulsen, Pernille},
  issn         = {1939-327X},
  language     = {eng},
  number       = {10},
  pages        = {2402--2408},
  publisher    = {American Diabetes Association Inc.},
  series       = {Diabetes},
  title        = {Regulation and Function of FTO mRNA Expression in Human Skeletal Muscle and Subcutaneous Adipose Tissue},
  url          = {http://dx.doi.org/10.2337/db09-0205},
  volume       = {58},
  year         = {2009},
}