Kynurenines: Tryptophan’s metabolites in exercise, inflammation, and mental health

Abstract

Kynurenine metabolites are generated by tryptophan catabolism and regulate biological processes that include host-microbiome signaling, immune cell response, and neuronal excitability. Enzymes of the kynurenine pathway are expressed in different tissues and cell types throughout the body and are regulated by cues, including nutritional and inflammatory signals. As a consequence of this systemic metabolic integration, peripheral inflammation can contribute to accumulation of kynurenine in the brain, which has been associated with depression and schizophrenia. Conversely, kynurenine accumulation can be suppressed by activating kynurenine clearance in exercised skeletal muscle. The effect of exercise training on depression through modulation of the kynurenine pathway highlights an important mechanism of interorgan cross-talk mediated by these metabolites. Here, we discuss peripheral mechanisms of tryptophan-kynurenine metabolism and their effects on inflammatory, metabolic, oncologic, and psychiatric disorders.

Melatonin alleviates adipose inflammation through elevating α‐ketoglutarate and diverting adipose‐derived exosomes to macrophages in mice

“…Considering the similar results in HFD and chow diets, we hypothesized that melatonin might affect important metabolites in both steady and stress state. Recently, studies confirm that the metabolites can contribute to the maintenance of cellular homeostasis and have important roles in inflammation and immune response . In addition, we found melatonin also elevated the cellular levels of citrate and αKG in adipose tissue.…”

Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects

“…Trp is a substrate for the generation of several bioactive compounds with various important physiological roles including anabolic processes, yet the majority of Trp is metabolized along the Kyn pathway (Cervenka et al 2017). This pathway is critical as it generates a range of metabolites that are involved in the interface of inflammatory/immune response and glutamatergic neurotransmission (Miller 2013).…”

Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives

“…Most of the dietary tryptophan is absorbed in the small intestine via large neutral amino acid transporters and enters the portal circulation to be metabolized in the liver. Kynurenine and kynurenine acid are important intermediates in the kynurenine pathway and have been implicated as biomarkers for MDD [40]. Tryptophan is metabolized by the intestinal microbiota to a variety of compounds including indoles that have been associated with cardiovascular disease [41].…”