Kynurenic Acid Acts as a Signaling Molecule Regulating Energy Expenditure and Is Closely Associated With Metabolic Diseases.

Delong Zhen,Zehua Song,Xu Dong Zhang,Junjun Liu

doi:10.3389/fendo.2022.847611

Abstract

Kynurenic acid (KYNA) is an important bio-active product of tryptophan metabolism. In addition to its well-known neuroprotective effects on mental health disorders, it has been proposed as a bio-marker for such metabolic diseases as atherosclerosis and diabetes. Emerging evidence suggests that KYNA acts as a signaling molecule controlling the networks involved in the balance of energy store and expenditure through GPR35 and AMPK signaling pathway. KYNA plays an important role in the pathogenesis and development of several endocrine and metabolic diseases. Exercise training promotes KYNA production in skeletal muscles and increases thermogenesis in the long term and limits weight gain, insulin resistance and inflammation. Additionally, KYNA is also present in breast milk and may act as an anti-obesity agent in infants. Although we are far from fully understanding the role of KYNA in our body, administration of KYNA, enzyme inhibitors or metabolites may serve as a potential therapeutic strategy for treating metabolic diseases. The present review provides a perspective on the current knowledge regarding the biological effects of KYNA in metabolic diseases and perinatal nutrition.

Highlights

Kynurenic acid (KYNA) is one of the metabolites of tryptophan catabolism formed via the kynurenine pathway
A large number of studies have been carried out to investigate the role of KYNA in the physio-pathology of central nervous system (CNS) such as depression, Alzheimer’s diseases and schizophrenia in the past two decades
For 3Methylglutaric acid (3MGA) which accumulates in the brains of children coursing with metabolic acidurias, experiments showed that 3MGA induced an increase in ROS production and lipid peroxidation and a decrease in mitochondrial function

Summary

Introduction

Kynurenic acid (KYNA) is one of the metabolites of tryptophan catabolism formed via the kynurenine pathway. The activation of KYNA production was not restrained in resident immune cells of adipose tissue as the increased expression of IDO1, KYAT2 and KYAT3 can be found in adipocytes. Liver seems to be another important source of serum KYNA in overweight individuals as TDO and KYATs are highly expressed in this organ [17, 18].

Results

Conclusion