Impact of the peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta) Ala203Pro polymorphism on in vivo metabolism, PGC-1beta expression and fibre type composition in human skeletal muscle.
OBJECTIVE
Peroxisome proliferator activated receptor-gamma coactivator-1beta (PGC-1beta, 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-1beta gene is associated with obesity. The aim of this study was to investigate whether the PGC-1beta Ala203Pro polymorphism influences the age-related decline in skeletal muscle PGC-1beta expression, in vivo metabolism and markers for muscle fibre type composition.


METHODS
The PGC-1beta 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-1beta 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-1beta 203Pro allele was positively related to insulin-stimulated NOGM and GF in the young twins. While muscle expression of PGC-1beta was reduced in elderly compared with young carriers of the Ala/Ala genotype (p < or = 0.001), there was no significant age-related decline in PGC-1beta expression in carriers of the 203Pro allele (p > or = 0.4). However, a regression analysis, correcting for covariates, showed that only age was significantly related to muscle PGC-1beta expression. Finally, PGC-1beta expression correlated positively with markers for oxidative fibres in human muscle.


CONCLUSIONS
This study suggests that young carriers of a PGC-1beta 203Pro allele have enhanced insulin-stimulated glucose metabolism and may be protected against an age-related decline in PGC-1beta expression in muscle.
Ling
C
C
Department of Clinical Sciences/Diabetes and Endocrinology, Lund University, CRC, University Hospital MAS, 205 02 Malmo, Sweden. charlotte.ling@med.lu.se
Wegner
L
L
Andersen
G
G
Almgren
P
P
Hansen
T
T
Pedersen
O
O
Groop
L
L
Vaag
A
A
Poulsen
P
P
D000328:Adult; D000367:Age Factors; D002352:Carrier Proteins / Q000235:genetics*; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D014427:Twins / Q000235:genetics
D002352:Carrier Proteins; C455622:PPARGC1B protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D005947:Glucose