Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome
Harald Mangge, Kelli L Summers, Andreas Meinitzer, Sieglinde Zelzer, Gunter Almer, Ruth Prassl, Wolfgang J Schnedl, Eva Reininghaus, Katharina Paulmichl, Daniel Weghuber, Dietmar Fuchs, Harald Mangge, Kelli L Summers, Andreas Meinitzer, Sieglinde Zelzer, Gunter Almer, Ruth Prassl, Wolfgang J Schnedl, Eva Reininghaus, Katharina Paulmichl, Daniel Weghuber, Dietmar Fuchs
Abstract
Objective: 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.
Results: 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.
Conclusions: 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.
Copyright © 2013 The Obesity Society.
Source: PubMed