IDO chronic immune activation and tryptophan metabolic pathway : a potential pathophysiological link between depression and obesity

• Author(s): Chaves Filho, Adriano José Maia ; Lima, Camila Nayane Carvalho ; Vasconcelos, Silvânia Maria Mendes ; Lucena, David Freitas de ; Maes, Michael ; Macedo, Danielle
• Date: 2017
• Origin: Oasisbr
• Subject(s): Obesidade; Depressão; Depression
• Document Type: Journal article
• Language: English

Description

Obesity and depression are among the most pressing health problems in the contemporary world. Obesity and depression share a bidirectional relationship, whereby each condition increases the risk of the other. By in- ference, shared pathways may underpin the comorbidity between obesity and depression. Activation of cell- mediated immunity (CMI) is a key factor in the pathophysiology of depression. CMI cytokines, including IFN- γ , TNF α and IL-1 β , induce the catabolism of tryptophan (TRY) by stimulating indoleamine 2,3-dioxygenase (IDO) resulting in the synthesis of kynurenine (KYN) and other tryptophan catabolites (TRYCATs). In the CNS, TRYCATs have been related to oxidative damage, in fl ammation, mitochondrial dysfunction, cytotoxicity, ex- citotoxicity, neurotoxicity and lowered neuroplasticity. The pathophysiology of obesity is also associated with a state of aberrant in fl ammation that activates aryl hydrocarbon receptor (AHR), a pathway involved in the de- tection of intracellular or environmental changes as well as with increases in the production of TRYCATs, being KYN an agonists of AHR. Both AHR and TRYCATS are involved in obesity and related metabolic disorders. These changes in the TRYCAT pathway may contribute to the onset of neuropsychiatric symptoms in obesity. This paper reviews the role of immune activation, IDO stimulation and increased TRYCAT production in the pa- thophysiology of depression and obesity. Here we suggest that increased synthesis of detrimental TRYCATs is implicated in comorbid obesity and depression and is a new drug target to treat both diseases.