First-Degree Relatives of Type 2 Diabetic Patients Have Reduced Expression of Genes Involved in Fatty Acid Metabolism in Skeletal Muscle.
(2012) In Journal of Clinical Endocrinology and Metabolism 97(7). p.1332-1337- Abstract
- 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,... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2609276
- author
- organization
-
- Translational Muscle Research (research group)
- Diabetes - Epigenetics (research group)
- Human Movement: health and rehabilitation (research group)
- Genetic and Molecular Epidemiology (research group)
- Clinical Physiology and Nuclear Medicine, Malmö (research group)
- Vascular Diseases - Clinical Research (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- EpiHealth: Epidemiology for Health
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Clinical Endocrinology and Metabolism
- volume
- 97
- issue
- 7
- pages
- 1332 - 1337
- publisher
- Oxford University Press
- external identifiers
-
- wos:000306286100034
- pmid:22547424
- scopus:84863560008
- pmid:22547424
- ISSN
- 1945-7197
- DOI
- 10.1210/jc.2011-3037
- project
- Fysik aktivitet, träning och kost vid typ 2 diabetes
- language
- English
- LU publication?
- yes
- id
- f7664e35-13ae-426c-9fc6-84f776c1929e (old id 2609276)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22547424?dopt=Abstract
- date added to LUP
- 2016-04-01 11:13:21
- date last changed
- 2024-04-08 02:37:22
@article{f7664e35-13ae-426c-9fc6-84f776c1929e, abstract = {{Context:<br/><br> 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.<br/><br> <br/><br> Objective:<br/><br> 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.<br/><br> <br/><br> Results:<br/><br> 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.<br/><br> <br/><br> Conclusions:<br/><br> 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.}}, author = {{Elgzyri, Targ and Parikh, Hemang and Zhou, Yuedan and Dekker Nitert, Marloes and Rönn, Tina and Segerström, Å B and Ling, Charlotte and Franks, Paul and Wollmer, Per and Eriksson, Karl-Fredrik and Groop, Leif and Hansson, Ola}}, issn = {{1945-7197}}, language = {{eng}}, number = {{7}}, pages = {{1332--1337}}, publisher = {{Oxford University Press}}, series = {{Journal of Clinical Endocrinology and Metabolism}}, title = {{First-Degree Relatives of Type 2 Diabetic Patients Have Reduced Expression of Genes Involved in Fatty Acid Metabolism in Skeletal Muscle.}}, url = {{http://dx.doi.org/10.1210/jc.2011-3037}}, doi = {{10.1210/jc.2011-3037}}, volume = {{97}}, year = {{2012}}, }