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Obesity‐related dysregulation of the Tryptophan–Kynurenine metabolism: Role of age and parameters of the metabolic syndrome
Author(s) -
Mangge Harald,
Summers Kelli L.,
Meinitzer Andreas,
Zelzer Sieglinde,
Almer Gunter,
Prassl Ruth,
Schnedl Wolfgang J.,
Reininghaus Eva,
Paulmichl Katharina,
Weghuber Daniel,
Fuchs Dietmar
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20491
Subject(s) - medicine , kynurenine , endocrinology , obesity , metabolic syndrome , tryptophan , overweight , inflammation , body mass index , neopterin , chemistry , amino acid , biochemistry
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.