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

Abstract

Aims/hypothesis: Peroxisome proliferator activated receptor-γ coactivator-1β (PGC-1β, also known as PPARGC1B) expression is reduced in skeletal muscle from patients with type 2 diabetes mellitus and in elderly subjects. Ala203Pro, a common variant in the PGC-1β gene is associated with obesity. The aim of this study was to investigate whether the PGC-1β Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1β expression, in vivo metabolism and markers for muscle fibre type composition. Materials and methods: The PGC-1β Ala203Pro polymorphism 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-1β 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-1β 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1β 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-1β 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-1β expression. Finally, PGC-1β expression correlated positively with markers for oxidative fibres in human muscle. Conclusions/interpretation: This study suggests that young carriers of a PGC-1β 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1β expression in muscle. © 2007 Springer-Verlag.