An exonic peroxisome proliferator-activated receptor-γ coactivator-1α variation may mediate the resting energy expenditure through a potential regulatory role on important gene expression in this pathway.
OBJECTIVE
We studied peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) gene variations at the 23815227-23815706 positions and examined their possible correlation with obesity-related conditions and resting energy expenditure (REE). We investigated the expression of PPARGC1A, mitogen-activated protein kinase (MAPK) and uncoupling protein 2 (UCP2), which play key roles in cellular energy expenditure, in a cellular model consisting of peripheral blood mononuclear cells, and compared them with various genotypes of the PPARGC1A gene.


METHODS
In total, 100 normal-weight and 129 obese subjects participated in the current study. All subjects were assessed for REE and body composition. We sequenced the PPARGC1A gene. Real-time PCR was used for determining the PPARGC1A, MAPK, and UCP2 gene expression.


RESULTS
There were significant differences in terms of body mass index, fat mass, low-density lipoprotein, insulin levels, REE/kg body weight, and REE/lean body mass among rs17574213 genotypes. There were significant differences in total cholesterol and low-density lipoprotein cholesterol levels among the various genotypes of Gly482Ser (rs8192678) and rs3755863. The relative PPARGC1A, MAPK, and UCP2 gene expressions had similar trends in the two studied SNPs, and the expression level of these genes was lowest in the TT genotype of Gly482Ser and rs3755863 and highest in the CC genotype of Gly482Ser and rs3755863.


CONCLUSIONS
Our findings suggest that PPARGC1A variations may influence PPARGC1A expression and the coordinating regulators of downstream targets in energy homeostasis. Further study is needed to shed some light on this process.
Bionanotechnology Group, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Khadijeh
K
Mirzaei
Arash
A
Hossein-nezhad
Solaleh
S
Emamgholipour
Hasti
H
Ansar
Mahtab
M
Khosrofar
Ali
A
Tootee
Soudabeh
S
Alatab
D000328:Adult; D001483:Base Sequence; D001823:Body Composition; D016022:Case-Control Studies; D017931:DNA Primers; D004734:Energy Metabolism / Q000235:genetics*; D005091:Exons; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics*
D017931:DNA Primers; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors