Dysregulation of Tryptophan Catabolism in Metabolic Syndrome

Obesity and metabolic syndrome are preventable complex-multifactorial disorders that severely increase risk of cardiovascular disease (CVD). Indoleamine 2,3-dioxygenase (IDO) enzyme converts tryptophan (TRP) to kynurenine (KYN); besides, KYN/TRP ratio has been shown to predict major coronary events and all-cause mortality in patients with coronary artery disease. However, their role in metabolic syndrome is not understood.

In a cross-sectional study (n = 161, mean population age in years = 32 ± 7.5, and sex = 53% female), standard anthropometric parameters, blood chemistry, high-sensitivity C-reactive protein, TRP, KYN, and KYN/TRP ratio were measured and compared with uric acid (UA), metabolic syndrome, and body mass index (BMI).

KYN/TRP ratio was significantly elevated in individuals with hyperuricemia (UA ≥7) (P < 0.0001), metabolic syndrome (P = 0.0066), and obesity (P = 0.0349), compared to their respective control groups. Moreover, increased presence of TRP does not correlate with increased TRP conversion to KYN, thus inflammation drives IDO enzyme activity. KYN/TRP levels were positively correlated with UA (R² = 0.1083, P < 0.0001), BMI (R² = 0.05267, P = 0.0036), and triglycerides (R² = 0.08053, P = 0.0003). Receiver operating characteristic curve implied that KYU/TRP ratio (AUC 0.7032, P < 0.0001) was more effective in stratifying CVD risk in combination with UA, and a gamma regression model (P < 0.001) demonstrated dependence of UA, BMI, and low-density lipoprotein along with KYN/TRP in CVD risk.

TRP catabolism is altered in metabolic syndrome; however, further studies are needed to understand role of kynurenine in pathology and disease outcomes.