Associations Among Obesity, Inflammation, and Tryptophan Catabolism in Pregnancy

Abstract

Objective: To evaluate relationships among obesity in pregnancy and plasma levels of tryptophan (TRP) and kynurenine (KYN), inflammatory markers, and depressed mood. Methods: Pregnant women ( N = 374) were enrolled, and data were collected at a mean gestation of 20 weeks in this cross-sectional study. Plasma was analyzed for TRP, KYN, neopterin, and nitrite levels. Women completed demographic and mood scales. Results: There was a statistically significant inverse correlation between body mass index (BMI) and TRP and positive correlations between BMI and KYN and the kynurenine/tryptophan (KYN/TRP) ratio. Neopterin was correlated with KYN/TRP, suggesting that the indoleamine 2,3-dioxygenase-1 (IDO-1) enzyme was activated. The correlations of neopterin and nitrite with BMI were too small to be clinically meaningful but may provide mechanistic insight. There was a correlation between depressed mood and nitrite levels. Depressed mood was also associated with lower TRP levels. When the sample was divided into pregnant women with or without obesity, TRP was significantly lower and the KYN/TRP ratio was significantly higher in the women with obesity. Conclusion: The pro-inflammatory state of obesity in pregnancy may drive activation of IDO-1, resulting in diversion of TRP away from serotonin and melatonin production and toward KYN metabolites. This alteration could contribute to depression, impaired sleep, increased production of excitotoxic neurotransmitters, and reinforcement of a pro-inflammatory state in pregnancy.