Department of Internal Medicine, MUMC, Maastricht, Netherlands.
CARIM, MUMC, Maastricht, Netherlands.
J Diabetes Res. 2019 May 14;2019:6289831. doi: 10.1155/2019/6289831. eCollection 2019.
Advanced glycation end products (AGEs) accumulate in fatty livers and may contribute to low-grade inflammation (LGI), potentially via their receptor, RAGE. It is unknown if the AGE accumulation in fatty livers results in elevated circulating AGEs. In a cohort study, we investigated the association of liver fat and hepatocellular damage with circulating AGEs and soluble RAGE (sRAGE) and subsequently the association of circulating AGEs and sRAGE with LGI. Cross-sectional associations of liver fat percentage (eLF%; ln-transformed) and liver enzymes (LE score; standardized) with circulating AGEs (free CML, CEL, and MG-H1 in nM and protein-bound CML, CEL, and pentosidine in nmol/mmol lysine; ln-transformed) and sRAGE (pg/ml, ln-transformed) and additionally of AGEs and sRAGE with LGI (standardized) were determined by multiple linear regression. eLF% was positively associated with circulating free CEL ( = 0.090; 95% CI 0.041; 0.139) but inversely with protein-bound CML ( = -0.071; 95% CI -0.108; -0.034). Similarly, the LE score was positively associated with free CML ( = 0.044; 95% CI 0.012; 0.076) and CEL ( = 0.040; 95% CI 0.009; 0.072) but inversely with protein-bound CML ( = -0.037; 95% CI -0.060; -0.013). Free CML ( = 0.297; 95% CI 0.049; 0.545) was positively associated with LGI, while protein-bound CML ( = -0.547; 95% CI -0.888; -0.207) was inversely associated, although this association was absent after adjustment for BMI. eLF% and LE score were not associated with sRAGE and sRAGE not with LGI after adjustment for BMI. Liver fat and enzymes were positively associated with circulating free AGEs, which were associated with LGI. In contrast, inverse relations were observed of liver fat and enzymes with circulating protein-bound AGEs and of protein-bound AGEs with LGI. These data suggest that hepatic steatosis and inflammation affect the formation and degradation of hepatic protein-bound AGEs resulting in elevated circulating free AGE levels. These alterations in AGE levels might influence LGI, but this is likely independent of RAGE.
晚期糖基化终产物 (AGEs) 在脂肪性肝脏中蓄积，并可能通过其受体 RAGE 导致低度炎症 (LGI)。目前尚不清楚脂肪性肝脏中 AGE 的蓄积是否会导致循环 AGE 水平升高。在一项队列研究中，我们研究了肝脂肪和肝细胞损伤与循环 AGEs 和可溶性 RAGE (sRAGE) 的相关性，随后研究了循环 AGEs 和 sRAGE 与 LGI 的相关性。通过多元线性回归，确定了肝脂肪百分比 (eLF%；ln 转换) 和肝酶 (LE 评分；标准化) 与循环 AGEs (游离 CML、CEL 和 MG-H1，以 nM 表示；蛋白结合 CML、CEL 和戊糖，以 nmol/mmol 赖氨酸表示；ln 转换) 和 sRAGE (pg/ml，ln 转换) 的横断面相关性，此外还确定了 AGEs 和 sRAGE 与 LGI (标准化) 的相关性。eLF% 与游离 CEL 呈正相关 ( = 0.090；95%CI 0.041；0.139)，与蛋白结合 CML 呈负相关 ( = -0.071；95%CI -0.108；-0.034)。同样，LE 评分与游离 CML ( = 0.044；95%CI 0.012；0.076) 和 CEL ( = 0.040；95%CI 0.009；0.072) 呈正相关，但与蛋白结合 CML 呈负相关 ( = -0.037；95%CI -0.060；-0.013)。游离 CML ( = 0.297；95%CI 0.049；0.545) 与 LGI 呈正相关，而蛋白结合 CML ( = -0.547；95%CI -0.888；-0.207) 呈负相关，但在调整 BMI 后，这种相关性不存在。调整 BMI 后，eLF% 和 LE 评分与 sRAGE 无关，sRAGE 与 LGI 无关。肝脂肪和酶与循环游离 AGEs 呈正相关，而游离 AGEs 与 LGI 相关。相反，肝脂肪和酶与循环蛋白结合 AGEs 呈负相关，而蛋白结合 AGEs 与 LGI 呈负相关。这些数据表明，肝脂肪变性和炎症影响肝蛋白结合 AGEs 的形成和降解，导致循环游离 AGE 水平升高。这些 AGE 水平的变化可能会影响 LGI，但这可能与 RAGE 无关。
