Procarcinogenic Characteristics of Tryptophan Metabolism in Obese Patients

Abstract

Tryptophan is an essential amino acid, the catabolism of which occurs in the human body along three main pathways: kynurenine, serotonin, and indole. At the same time, a significant part of tryptophan metabolites is formed as a result of the enzymatic activity of the intestinal microbiota. Deviations in tryptophan metabolism, manifested in the form of shifts towards the formation of certain metabolites, are characteristic of some pathological conditions, in particular obesity and malignant neoplasms. It is known that the growth of some types of tumors is associated with excess body weight, but the mechanisms of the procarcinogenic effect of obesity remain not fully understood. Obesity is characterized by the development of systemic inflammation and increased production of proinflammatory cytokines, which increase the expression of the key enzyme of the kynurenine pathway and intensify the formation of immunosuppressive and cytotoxic metabolites: kynurenine and quinolinic acid. Increased stimulation of the kynurenine pathway in the body of obese and cancer patients leads to a decrease in tryptophan itself, which is necessary for the proliferation of immunocompetent cells and a normal immune response. Both obese and cancer patients are characterized by increased levels of quinolinic acid and decreased concentrations of indole-3-propionate in the blood serum. Obese patients are often characterized by a decrease in serotonin in the blood serum, while not only an increase in serotonin production has been established for tumor tissues but also an increase in the expression of various types of serotonin receptors. The existing general trends in changes in tryptophan metabolism indicate the presence of intersection points in the pathogenesis of obesity and tumor development. A literature review was conducted using the PubMed database, primarily using literature sources from 2018–2024.