Your browser has javascript turned off or blocked. This will lead to some parts of our website to not work properly or at all. Turn on javascript for best performance.

The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Paul Franks

Paul Franks

Principal investigator

Paul Franks

First-Degree Relatives of Type 2 Diabetic Patients Have Reduced Expression of Genes Involved in Fatty Acid Metabolism in Skeletal Muscle.

Author

  • Targ Elgzyri
  • Hemang Parikh
  • Yuedan Zhou
  • Marloes Dekker Nitert
  • Tina Rönn
  • Å B Segerström
  • Charlotte Ling
  • Paul Franks
  • Per Wollmer
  • Karl-Fredrik Eriksson
  • Leif Groop
  • Ola Hansson

Summary, in English

Context:

First-degree relatives of patients with type 2 diabetes (FH+) have been shown to have decreased energy expenditure and decreased expression of mitochondrial genes in skeletal muscle. In previous studies, it has been difficult to distinguish whether mitochondrial dysfunction and differential regulation of genes are primary (genetic) or due to reduced physical activity, obesity, or other correlated factors.



Objective:

The aim of this study was to investigate whether mitochondrial dysfunction is a primary defect or results from an altered metabolic state.Design:We compared gene expression in skeletal muscle from 24 male subjects with FH and 26 without FH matched for age, glucose tolerance, VO(2peak) (peak oxygen uptake), and body mass index using microarrays. Additionally, type fiber composition, mitochondrial DNA content, and citrate synthase activity were measured. The results were followed up in an additional cohort with measurements of in vivo metabolism.



Results:

FH+vs. FH- subjects showed reduced expression of mitochondrial genes (P = 2.75 x 10(-6)), particularly genes involved in fatty acid metabolism (P = 4.08 x 10(-7)), despite similar mitochondrial DNA content. Strikingly, a 70% reduced expression of the monoamine oxidase A (MAOA) gene was found in FH+ vs. FH- individuals (P = 0.0009). Down-regulation of the genes involved in fat metabolism was associated with decreased in vivo fat oxidation and increased glucose oxidation examined in an additional cohort of elderly men.



Conclusions:

These results suggest that genetically altered fatty acid metabolism predisposes to type 2 diabetes and propose a role for catecholamine-metabolizing enzymes like MAOA in the regulation of energy metabolism.

Department/s

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Epigenetics
  • Physiotherapy
  • Genetic and Molecular Epidemiology
  • Clinical Physiology, Malmö
  • Vascular Diseases - Clinical Research
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year

2012

Language

English

Pages

1332-1337

Publication/Series

Journal of Clinical Endocrinology and Metabolism

Volume

97

Issue

7

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Diabetes - Epigenetics
  • Physiotherapy
  • Genetic and Molecular Epidemiology
  • Clinical Physiology, Malmö
  • Vascular Diseases - Clinical Research

ISBN/ISSN/Other

  • ISSN: 1945-7197