Obesity-related dysregulation of the Tryptophan–Kynurenine metabolism: Role of age and parameters of the metabolic syndrome
Funding agencies: This work was funded by the “Zukunftsfond Steiermark” Project “STYJOBS”. Furthermore, this work was partially supported by the Austrian Science Fund (FWF) grant No. P20455.
Disclosure: The authors declared no conflict of interest.
Obesity-related immune mediated systemic inflammation was associated with the development of the metabolic syndrome by induction of the tryptophan (TRP)–kynurenine (KYN) pathway. The study aimed to assess whether this holds true across the lifespan from juvenility to adulthood.
Design and Methods
Five hundred twenty-seven participants aged between 10 and 65 years were analyzed. Standard anthropometric measures, carotid ultrasound, and laboratory analysis including interleukin-6, ultra-sensitive C-reactive protein, lipids, glucose metabolism, neopterin, TRP, KYN levels, and the KYN/TRP ratio were performed.
Overweight/obese (ow/ob) adults had significantly increased KYN serum levels and a significantly increased KYN/TRP ratio. In sharp contrast, ow/ob juvenile males aged ≤18 years showed decreased, females similar KYN and KYN/TRP ratio in comparison to their control counterparts. Also, adult ow/ob subjects with metabolic syndrome showed markedly increased KYN/TRP ratios contrary to decreased KYN/TRP ratios in ow/ob juveniles. Abdominal fat content, characterized by age normalized waist circumference, and not body mass index, had the strongest effect for an increase of the KYN/TRP ratio in adults.
TRP metabolism and obesity-related immune mediated inflammation differs markedly between juveniles and adults. While childhood obesity seems to be dominated by a Th2-driven activation, an accelerated production of Th1-type cytokines may pave the way for later atherosclerotic endpoints.