title: Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome.
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.
  
  
  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.
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Research Unit on Lifestyle and Inflammation-associated Risk Biomarkers, Medical University of Graz, Graz, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Mangge
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Summers
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Sieglinde
authors.initials: S
authors.lastname: Zelzer
authors.forename: Gunter
authors.initials: G
authors.lastname: Almer
authors.forename: Ruth
authors.initials: R
authors.lastname: Prassl
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Schnedl
authors.forename: Eva
authors.initials: E
authors.lastname: Reininghaus
authors.forename: Katharina
authors.initials: K
authors.lastname: Paulmichl
authors.forename: Daniel
authors.initials: D
authors.lastname: Weghuber
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007737:Kynurenine / Q000097:blood*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D008875:Middle Aged; D019798:Neopterin / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000150:complications / Q000503:physiopathology; D064887:Observational Studies as Topic; D014364:Tryptophan / Q000097:blood*; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D007737:Kynurenine; D019798:Neopterin; D014364:Tryptophan; D002097:C-Reactive Protein