The role of polymorphism of redox-sensitive genes in the mechanisms of oxidative stress in obesity and metabolic diseases

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Abstract

The review summarizes ideas about the role of polymorphic variants of redox-sensitive genes that regulate the development of oxidative stress in obesity and associated metabolic diseases. The concept of oxidative stress, activated oxygen metabolites (AOM), which include reactive forms of oxygen, nitrogen, and chlorine, is considered, and an idea of the antioxidant system and its enzymatic link is given. The important role of gene polymorphism of AOM-producing enzymes — CYBA, CYBB, MT-ND1/2/4L, MT-CO1/3, XOR, CYP, NOS2/3, MPO — in the induction of oxidative stress in obesity has been shown. The dualism of AOM in obesity is emphasized: on the one hand, they are necessary for normal adipogenesis and signaling, and, on the other hand, they play a trigger role in the development of oxidative stress. It has been demonstrated that an imbalance in antioxidant system in obesity and metabolic disorders may be associated with variability in the genes of key antioxidant enzymes and proteins — SOD1/2/3, CAT, GPX1-8, GSR, GSTP1, GSTM1, GSTT1, PRDX3, TXNIP, HMOX1, NQO1, NFE2L2, KEAP1. The critical role of polymorphism in the Nrf2 transcription factor gene, the main regulator of redox homeostasis under physiological conditions and in obesity, has been demonstrated. It has been demonstrated that disruption of redox homeostasis due to genetic variability of the prooxidant-antioxidant system contributes to the development of the pathological obesity phenotype. Understanding the genetic mechanisms underlying oxidative stress in obesity and metabolic diseases is necessary to expand knowledge about the mechanisms of pathogenesis of these diseases and to develop effective methods for their correction.

About the authors

Mikhail A. Shkurat

Southern Federal University

Email: mikhail@shkurat.com
ORCID iD: 0000-0002-9383-4607
SPIN-code: 4921-2480

research associate

Russian Federation, Rostov-on-Don

Elena V. Mashkina

Southern Federal University

Author for correspondence.
Email: lenmash@mail.ru
ORCID iD: 0000-0002-4424-9508
SPIN-code: 3010-1500

Dr. Sci. (Biol.), professor of the Department of genetics

Russian Federation, Rostov-on-Don

Natalya P. Milyutina

Southern Federal University

Email: natmilut@rambler.ru
ORCID iD: 0000-0002-7522-3183
SPIN-code: 7228-8860

Cand. Sci. (Biol.), senior research associate

Russian Federation, Rostov-on-Don

Tatiana P. Shkurat

Southern Federal University

Email: tshkurat@yandex.ru
ORCID iD: 0000-0001-6197-7374
SPIN-code: 5620-2091

Dr. Sci. (Biol.), professor, head of the Department of genetics

Russian Federation, Rostov-on-Don

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Supplementary files

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2. Fig. 1. Composition of redox-sensitive genes and their role in the development of oxidative stress in obesity and metabolic diseases

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3. Fig. 2. Mechanisms of oxidative stress development in obesity and metabolic diseases

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