The incidence of obesity has increased over the last 30 years at a staggering rate worldwide. Eight percent of children and 16% of adults were classified as obese in 2022. Obesity increases the risk of comorbidities, including diabetes, cardiovascular disease, and steatotic liver diseases. The liver plays a major role in tryptophan metabolism and liver fibrosis is associated with increased kynurenine pathway activity. A recent study published by Dr. Carmen Arto and colleagues investigated kynurenine pathway metabolite levels in obese individuals with and without metabolic dysfunction-associated steatotic liver disease (MASLD).
Body mass index (BMI) was significantly associated with quinolinic acid (QUIN), kynurenic acid, and 5-hydroxy-L-tryptophan levels. Furthermore, individuals classified as obese (BMI >40 kg/m2) had significantly higher plasma levels of these metabolites when compared to individuals with normal weight. With liver steatosis kynurenine pathway activity increased, resulting in elevated levels of kynurenine and QUIN. Obese individuals with MASLD had higher levels of plasma tryptophan as well as increased KMO and IDO gene expression within the liver. This suggests that the kynurenine pathway and liver pathology can influence one another and point to potential therapeutic targets for MASLD.