Obesity (Silver Spring, Md.) · 2013
Obesity-related dysregulation of the tryptophan-kynurenine metabolism: role of age and parameters of the metabolic syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Mangge Harald, Summers Kelli L, Meinitzer Andreas, Zelzer Sieglinde, Almer Gunter, Prassl Ruth, Schnedl Wolfgang J, Reininghaus Eva, Paulmichl Katharina, Weghuber Daniel, Fuchs Dietmar
Аннотация
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.
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.