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

Elgzyri, Targ LU ; Parikh, Hemang; Zhou, Yuedan LU ; Dekker Nitert, Marloes LU ; Rönn, Tina LU ; Segerström, A B; Ling, Charlotte LU ; Franks, Paul LU ; Wollmer, Per LU and Eriksson, Karl-Fredrik LU , et al. (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)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Clinical Endocrinology and Metabolism
volume
97
issue
7
pages
1332 - 1337
publisher
The Endocrine Society
external identifiers
  • wos:000306286100034
  • pmid:22547424
  • scopus:84863560008
ISSN
1945-7197
DOI
10.1210/jc.2011-3037
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
2012-06-01 13:15:51
date last changed
2017-09-10 03:28:59
@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, A 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    = {The Endocrine Society},
  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},
  volume       = {97},
  year         = {2012},
}