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

Abstract

Background/Aims: 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.