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Karl-Fredrik Eriksson

Associate professor

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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.

Author

  • Anders H Olsson
  • Tina Rönn
  • Tarq Elgzyri
  • Ola Hansson
  • Karl-Fredrik Eriksson
  • Leif Groop
  • Allan Vaag
  • Pernille Poulsen
  • Charlotte Ling

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Vascular Diseases - Clinical Research

Publishing year

2011

Language

English

Pages

275-281

Publication/Series

Molecular Genetics and Metabolism

Volume

103

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Vascular Diseases - Clinical Research

ISBN/ISSN/Other

  • ISSN: 1096-7192