Clinical Institute of Medical and Chemical Laboratory Diagnostics, Research Unit on Lifestyle and Inflammation-associated Risk Biomarkers, Medical University of Graz, Graz, Austria.
Obesity (Silver Spring). 2014 Jan;22(1):195-201. doi: 10.1002/oby.20491. Epub 2013 Jul 5.
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.
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.
肥胖相关的免疫介导的全身炎症通过诱导色氨酸(TRP)-犬尿氨酸(KYN)途径与代谢综合征的发展相关。本研究旨在评估从青少年到成年的整个生命周期中是否存在这种情况。
分析了 527 名年龄在 10 至 65 岁之间的参与者。进行了标准的人体测量学测量、颈动脉超声检查以及实验室分析,包括白细胞介素-6、超敏 C 反应蛋白、脂质、葡萄糖代谢、新蝶呤、TRP、KYN 水平和 KYN/TRP 比值。
超重/肥胖(ow/ob)成年人的血清 KYN 水平显著升高,KYN/TRP 比值显著升高。相比之下,≤18 岁的 ow/ob 青少年男性的 KYN 和 KYN/TRP 比值降低,女性则与对照组相似。此外,患有代谢综合征的成年 ow/ob 受试者的 KYN/TRP 比值明显升高,而 ow/ob 青少年的 KYN/TRP 比值则降低。以年龄标准化腰围而不是体重指数来衡量的腹部脂肪含量对成年人 KYN/TRP 比值的增加影响最大。
TRP 代谢和肥胖相关的免疫介导的炎症在青少年和成年人之间存在显著差异。虽然儿童肥胖似乎主要由 Th2 驱动的激活所主导,但 Th1 型细胞因子的加速产生可能为以后的动脉粥样硬化终点铺平道路。