Advanced

Impact of the peroxisome proliferator activated receptor-gamma coactivator-1 beta (PGC-1 beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1 beta expression and fibre type composition in human skeletal muscle

Ling, Charlotte LU ; Wegner, L.; Andersen, G.; Almgren, Peter LU ; Hansen, T.; Pedersen, O.; Groop, Leif LU ; Vaag, A. and Poulsen, P. (2007) In Diabetologia 50(8). p.1615-1620
Abstract
Aims/hypothesis Peroxisome proliferator activated receptor-gamma coactivator-lp (PGC-1 beta, also known as PPARGCIB) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1 beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1 beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1 beta expression, in vivo metabolism and markers for muscle fibre type composition. Materials and methods The PGC-1 beta Ala203Pro polymerphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1 beta expression, in vivo... (More)
Aims/hypothesis Peroxisome proliferator activated receptor-gamma coactivator-lp (PGC-1 beta, also known as PPARGCIB) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1 beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1 beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1 beta expression, in vivo metabolism and markers for muscle fibre type composition. Materials and methods The PGC-1 beta Ala203Pro polymerphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1 beta expression, in vivo metabolism and markers for fibre type composition. Results Insulin-stimulated non-oxidative glucose metabolism (NOGM; p=0.025) and glycolytic flux rate (GF; p=0.026) were reduced in young Ala/Ala carriers compared with carriers of a 203Pro allele. In addition, a regression analysis, correcting for covariates, showed that the PGC-1 beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1 beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p <= 0.001), there was no significant age-related decline in PGC-1 beta expression in carriers of the 203Pro allele (p >= 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1 beta expression. Finally, PGC-1 beta expression correlated positively with markers for oxidative fibres in human muscle. Conclusions/interpretation This study suggests that young carriers of a PGC-1 beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1 beta expression in muscle. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
in vivo metabolism, PGC-1 beta, skeletal muscle, polymorphism, fibre type, gene expression, PPARGC1B
in
Diabetologia
volume
50
issue
8
pages
1615 - 1620
publisher
Springer Verlag
external identifiers
  • wos:000248225100007
  • scopus:34447120855
ISSN
1432-0428
DOI
10.1007/s00125-007-0729-6
language
English
LU publication?
yes
id
111758a5-7b42-4a4e-8b9c-2c16974690f9 (old id 692724)
date added to LUP
2007-12-13 13:08:15
date last changed
2017-01-01 04:49:11
@article{111758a5-7b42-4a4e-8b9c-2c16974690f9,
  abstract     = {Aims/hypothesis Peroxisome proliferator activated receptor-gamma coactivator-lp (PGC-1 beta, also known as PPARGCIB) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1 beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1 beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1 beta expression, in vivo metabolism and markers for muscle fibre type composition. Materials and methods The PGC-1 beta Ala203Pro polymerphism was genotyped in 110 young (age 28.0 +/- 1.9 years) and 86 elderly (age 62.4 +/- 2.0 years) twins and related to muscle PGC-1 beta expression, in vivo metabolism and markers for fibre type composition. Results Insulin-stimulated non-oxidative glucose metabolism (NOGM; p=0.025) and glycolytic flux rate (GF; p=0.026) were reduced in young Ala/Ala carriers compared with carriers of a 203Pro allele. In addition, a regression analysis, correcting for covariates, showed that the PGC-1 beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1 beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p &lt;= 0.001), there was no significant age-related decline in PGC-1 beta expression in carriers of the 203Pro allele (p &gt;= 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1 beta expression. Finally, PGC-1 beta expression correlated positively with markers for oxidative fibres in human muscle. Conclusions/interpretation This study suggests that young carriers of a PGC-1 beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1 beta expression in muscle.},
  author       = {Ling, Charlotte and Wegner, L. and Andersen, G. and Almgren, Peter and Hansen, T. and Pedersen, O. and Groop, Leif and Vaag, A. and Poulsen, P.},
  issn         = {1432-0428},
  keyword      = {in vivo metabolism,PGC-1 beta,skeletal muscle,polymorphism,fibre type,gene expression,PPARGC1B},
  language     = {eng},
  number       = {8},
  pages        = {1615--1620},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Impact of the peroxisome proliferator activated receptor-gamma coactivator-1 beta (PGC-1 beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1 beta expression and fibre type composition in human skeletal muscle},
  url          = {http://dx.doi.org/10.1007/s00125-007-0729-6},
  volume       = {50},
  year         = {2007},
}