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Neuronal NO Synthase in the Pathogenesis of Metabolic Syndrome

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Abstract

In recent years, metabolic syndrome (MS), which is characterized by obesity, hypertension, dyslipidemia, and insulin resistance, has become an epidemic. Therefore, the study of the molecular mechanisms underlying the development of MS and its complications, as well as the search for new therapeutic agents for their treatment, is one of the most acute problems of modern endocrinology. In recent years, convincing evidence was obtained that functional changes in the expression, activity, and regulatory properties of neuronal NO synthase (nNOS), which catalyzes the formation of the essential secondary messenger (nitric oxide, NO), and the NO/cGMP-signaling pathways in the brain, myocardium, and skeletal muscles that depend upon it play a key role among molecular causes of MS. In the brain, nNOS is associated with NMDA receptors, hyperactivation of which in MS is accompanied by excessive nNOS stimulation and hyperproduction of NO, which leads to NO-induced damage of neurons and violation of the central regulation of physiological processes and neurodegeneration. In the myocardium, changes in the expression and localization of nNOS, as well as its functional interaction with cytoskeletal proteins, are noted in MS; this leads to disturbances in myocardial contraction and hypertrophy. In the skeletal muscles, nNOS controls their contraction and oxidative metabolism and is involved in the regulation of vascular relaxation, as well as in the regulation of glucose transport. A decrease in the expression and activity of nNOS, as well as dysregulation of its activity in MS, causes disturbances in these processes, making a significant contribution to the development of insulin resistance and deterioration of glucose homeostasis. Thus, nNOS can be considered an important therapeutic target in the treatment of MS and other metabolic disorders, as well as for preventing complications in the nervous and cardiovascular systems and locomotor apparatus.

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ACKNOWLEDGMENTS

The authors are grateful to A. S. Maslov for assistance in the design of figures.

Funding

This work was carried out within the framework of state assignment no. 075-00967-23-00 of the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences.

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  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223, St. Petersburg, Russia

    L. A. Kuznetsova, N. E. Basova & A. O. Shpakov

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  1. L. A. Kuznetsova
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  2. N. E. Basova
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Correspondence to L. A. Kuznetsova.

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Translated by A. Barkhash

Abbreviations: MS—metabolic syndrome; T2DM—type 2 diabetes mellitus; CVD—cardiovascular diseases; CaM—bound calmodulin; nitric oxide synthase—nNOS.

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Kuznetsova, L.A., Basova, N.E. & Shpakov, A.O. Neuronal NO Synthase in the Pathogenesis of Metabolic Syndrome. Cell Tiss. Biol. 17, 1–15 (2023). https://doi.org/10.1134/S1990519X23010108

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