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The expression of myosin heavy chain (MHC) genes in human skeletal muscle is related to metabolic characteristics involved in the pathogenesis of type 2 diabetes.

Olsson, Anders H LU ; Rönn, Tina LU ; Elgzyri, Tarq LU ; Hansson, Ola LU orcid ; Eriksson, Karl-Fredrik LU ; Groop, Leif LU ; Vaag, Allan LU ; Poulsen, Pernille and Ling, Charlotte LU (2011) In Molecular Genetics and Metabolism 103. p.275-281
Abstract
Type 2 diabetes patients exhibit a reduction in oxidative muscle fibres and an increase in glycolytic muscle fibres. In this study, we investigated whether both genetic and non-genetic factors influence the mRNA expression levels of three myosin heavy chain (MHC) genes represented in different fibre types. Specifically, we examined the MHC7 (slow-twitch oxidative fibre), MHCIIa (fast-twitch oxidative fibre) and MHCIIx/d (fast-twitch glycolytic fibre) genes in human skeletal muscle. We further investigated the use of MHC mRNA expression as a proxy to determine fibre-type composition, as measured by traditional ATP staining. Two cohorts of age-matched Swedish men were studied to determine the relationship of muscle mRNA expression of MHC7,... (More)
Type 2 diabetes patients exhibit a reduction in oxidative muscle fibres and an increase in glycolytic muscle fibres. In this study, we investigated whether both genetic and non-genetic factors influence the mRNA expression levels of three myosin heavy chain (MHC) genes represented in different fibre types. Specifically, we examined the MHC7 (slow-twitch oxidative fibre), MHCIIa (fast-twitch oxidative fibre) and MHCIIx/d (fast-twitch glycolytic fibre) genes in human skeletal muscle. We further investigated the use of MHC mRNA expression as a proxy to determine fibre-type composition, as measured by traditional ATP staining. Two cohorts of age-matched Swedish men were studied to determine the relationship of muscle mRNA expression of MHC7, MHCIIa, and MHCIIx/d with muscle fibre composition. A classical twin approach, including young and elderly Danish twin pairs, was utilised to examine if differences in expression levels were due to genetic or environmental factors. Although MHCIIx/d mRNA expression correlated positively with the level of type IIx/d muscle fibres in the two cohorts (P<0.05), a relatively low magnitude of correlation suggests that mRNA does not fully correlate with fibre-type composition. Heritability estimates and genetic analysis suggest that the levels of MHC7, MHCIIa and MHCIIx/d expression are primarily under non-genetic influence, and MHCIIa indicated an age-related decline. PGC-1α exhibited a positive relationship with the expression of all three MHC genes (P<0.05); meanwhile, PGC-1β related positively with MHCIIa expression and negatively with MHCIIx/d expression (P<0.05). While MHCIIa expression related positively with insulin-stimulated glucose uptake (P<0.01), MHCIIx/d expression related negatively with insulin-stimulated glucose uptake (P<0.05). Our findings suggest that the expression levels of the MHC genes are associated with age and both PGC-1α and PGC-1β and indicate that the MHC genes may to some extent be used to determine fibre-type composition in human skeletal muscle. (Less)
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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Genetics and Metabolism
volume
103
pages
275 - 281
publisher
Elsevier
external identifiers
  • wos:000291919500011
  • pmid:21470888
  • scopus:79958030339
  • pmid:21470888
ISSN
1096-7192
DOI
10.1016/j.ymgme.2011.03.017
language
English
LU publication?
yes
id
e8cbd6f3-90fd-4288-b5a9-d1cf2ab1d997 (old id 1937408)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21470888?dopt=Abstract
date added to LUP
2016-04-04 08:32:09
date last changed
2021-10-10 03:22:13
@article{e8cbd6f3-90fd-4288-b5a9-d1cf2ab1d997,
  abstract     = {Type 2 diabetes patients exhibit a reduction in oxidative muscle fibres and an increase in glycolytic muscle fibres. In this study, we investigated whether both genetic and non-genetic factors influence the mRNA expression levels of three myosin heavy chain (MHC) genes represented in different fibre types. Specifically, we examined the MHC7 (slow-twitch oxidative fibre), MHCIIa (fast-twitch oxidative fibre) and MHCIIx/d (fast-twitch glycolytic fibre) genes in human skeletal muscle. We further investigated the use of MHC mRNA expression as a proxy to determine fibre-type composition, as measured by traditional ATP staining. Two cohorts of age-matched Swedish men were studied to determine the relationship of muscle mRNA expression of MHC7, MHCIIa, and MHCIIx/d with muscle fibre composition. A classical twin approach, including young and elderly Danish twin pairs, was utilised to examine if differences in expression levels were due to genetic or environmental factors. Although MHCIIx/d mRNA expression correlated positively with the level of type IIx/d muscle fibres in the two cohorts (P&lt;0.05), a relatively low magnitude of correlation suggests that mRNA does not fully correlate with fibre-type composition. Heritability estimates and genetic analysis suggest that the levels of MHC7, MHCIIa and MHCIIx/d expression are primarily under non-genetic influence, and MHCIIa indicated an age-related decline. PGC-1α exhibited a positive relationship with the expression of all three MHC genes (P&lt;0.05); meanwhile, PGC-1β related positively with MHCIIa expression and negatively with MHCIIx/d expression (P&lt;0.05). While MHCIIa expression related positively with insulin-stimulated glucose uptake (P&lt;0.01), MHCIIx/d expression related negatively with insulin-stimulated glucose uptake (P&lt;0.05). Our findings suggest that the expression levels of the MHC genes are associated with age and both PGC-1α and PGC-1β and indicate that the MHC genes may to some extent be used to determine fibre-type composition in human skeletal muscle.},
  author       = {Olsson, Anders H and Rönn, Tina and Elgzyri, Tarq and Hansson, Ola and Eriksson, Karl-Fredrik and Groop, Leif and Vaag, Allan and Poulsen, Pernille and Ling, Charlotte},
  issn         = {1096-7192},
  language     = {eng},
  pages        = {275--281},
  publisher    = {Elsevier},
  series       = {Molecular Genetics and Metabolism},
  title        = {The expression of myosin heavy chain (MHC) genes in human skeletal muscle is related to metabolic characteristics involved in the pathogenesis of type 2 diabetes.},
  url          = {http://dx.doi.org/10.1016/j.ymgme.2011.03.017},
  doi          = {10.1016/j.ymgme.2011.03.017},
  volume       = {103},
  year         = {2011},
}