Genetics of oxidative stress in obesity

Abstract

Obesity is a multifactorial disease characterized by the excessive accumulation of fat in adipose tissue and peripheral organs. Its derived metabolic complications are mediated by the associated oxidative stress, inflammation and hypoxia. Oxidative stress is due to the excessive production of reactive oxygen species or diminished antioxidant defenses. Genetic variants, such as single nucleotide polymorphisms in antioxidant defense system genes, could alter the efficacy of these enzymes and, ultimately, the risk of obesity; thus, studies investigating the role of genetic variations in genes related to oxidative stress could be useful for better understanding the etiology of obesity and its metabolic complications. The lack of existing literature reviews in this field encouraged us to gather the findings from studies focusing on the impact of single nucleotide polymorphisms in antioxidant enzymes, oxidative stress-producing systems and transcription factor genes concerning their association with obesity risk and its phenotypes. In the future, the characterization of these single nucleotide polymorphisms (SNPs) in obese patients could contribute to the development of controlled antioxidant therapies potentially beneficial for the treatment of obesity-derived metabolic complications.

Figure 1.

A schematic diagram of the multifactorial character of obesity. These factors influence the development of obesity and its associated comorbidities by altering adipokine secretion, hypoxia and inflammation with associated oxidative stress. The presence of certain single nucleotide polymorphisms (SNPs) reviewed here can increase the risk of obesity and its comorbidities, further worsening the metabolic profile.

Figure 2.

Effects of the main known SNPs of the antioxidant defense system genes in the cell on obesity. Dark orange and green boxes indicate higher or lower obesity risk associated with the SNP, respectively. Light orange boxes indicate conflicting results. Red and green arrows matching the color of an allele of the SNP indicate higher or lower enzyme activity associated with that allele. Dashed green arrows indicate activation. CAT, catalase; CuZn-SOD, copper-zinc superoxide dismutase; ETC, electron transport chain; GPX, glutathione peroxidase; GSH, reduced glutathione; GSSG, oxidized glutathione; HDL, high-density lipoprotein; HFD, high-fat diet; Mn-SOD, manganese superoxide dismutase; MsrA, methionine sulphoxide reductase A; NADPH, nicotinamide adenine dinucleotide phosphate; NPGPX, non-selenocysteine-containing phospholipid hydroperoxide glutathione peroxidases; NRF2, nuclear erythroid factor 2-like 2; O₂^•−, superoxide; PGC1α, peroxisome proliferator-activated receptor γ coactivator-1α; PON1, paraoxonase 1; PPARγ, peroxisome proliferator activated receptor gamma; PRDX3, peroxiredoxin 3; TNFα, tumor necrosis factor alpha.