Advanced glycation end product: A potential biomarker for risk stratification of non-alcoholic fatty liver disease in ELSA-Brasil study

Abstract

BACKGROUND Liver diseases are associated with the excess formation of advanced glycation end products (AGEs), which induce tissue inflammation and oxidative damage. However, the trend of oxidative marker levels according to the steatosis grade in non-alcoholic fatty liver disease (NAFLD) is unclear. AIM To compare serum AGE levels between participants with NAFLD accordingly to steatosis severity in the baseline ELSA-Brasil population. METHODS In 305 individuals at baseline ELSA-Brasil, NAFLD-associated steatosis was classified by ultrasound hepatic attenuation. The participants were grouped according to the severity of steatosis: mild and moderate/severe pooled. The measurement of serum fluorescent AGE concentrations was based on spectrofluorimetric detection. Serum AGE content and clinical and laboratory characteristics of the participants were compared between groups. The correlation between serum AGE levels and the grade of steatosis was analyzed. Logistic regression analysis was used to investigate the relationship between serum AGE levels and steatosis severity. A P value < 0.05 was considered statistically significant. RESULTS According to the steatosis severity spectrum in NAFLD, from mild to moderate/severe, individuals with the most severe steatosis grade had a higher incidence of metabolic syndrome (63% vs 34%, P ≤ 0.001), diabetes mellitus (37% vs 14%, P ≤ 0.001), and high cholesterol levels (51% vs 33%, P < 0.001). Moreover, individuals with increasing severity of steatosis presented increasing waist circumference, body mass index, systolic and diastolic blood pressure, fasting blood glucose, glycated hemoglobin, insulin, triglycerides, alanine aminotransferase, gamma-glutamyl transferase, C-reactive protein, and uric acid levels and lower high-density lipoprotein. Higher serum AGE content was present in the moderate/severe group of individuals than in the mild group ( P = 0.008). In addition, the serum AGE levels were correlated with the steatosis grade in the overall sample (rho = 0.146, P = 0.010). Logistic regression analysis, after adjusting for confounding variables, showed that subjects with higher serum AGE content had a 4.6-fold increased chance of having moderate or severe steatosis when compared to low levels of serum AGEs. According to the results of the receiver operator characteristic curves analyses (areas under the curve, AUC = 0.83), AGEs could be a good marker of steatosis severity in patients with NAFLD and might be a potential biomarker in predicting NAFLD progression, strengthening the involvement of AGE in NAFLD pathogenesis. CONCLUSION NAFLD-associated steatosis was associated with serum AGE levels; therefore,...

Albumin, an interesting and functionally diverse protein, varies from ‘native’ to ‘effective’ (Review)

“…Whereafter AGEs can participate in the oxidative stress and inflammation of NAFLD by combining with the AGEs receptor (RAGE) to promote the occurrence of hepatic steatosis (hepatocyte steatosis) and even fibrosis and form a positive feedback loop (Table II) (125,126). This is consistent with the study by Pereira et al (127) that AGEs can monitor the progression of mild, moderate and severe NAFLD according to the grade of steatosis (127). Therefore, as aforementioned, in addition to HNA1 and HNA2, AGEs may also promote systemic inflammation in liver disease.…”

The Association between the Level of Advanced Glycation End Products and Objective Skin Quality Parameters

“…Through the multiligand receptor for advanced glycation end products (RAGE) on the vascular cells, AGEs play a key role in the inflammatory process [ 13 ]. It is well established that higher levels of AGEs are linked to diseases such as diabetes, chronic kidney disease, nonalcoholic fatty liver disease, obesity and cardiovascular diseases [ 14 , 15 , 16 , 17 , 18 , 19 ].…”

Dietary advanced glycation end products are associated with an increased risk of non-alcoholic fatty liver disease in Iranian adults

“…Hyogo et al [ 43 ] reported that serum levels of AGEs increased in patients diagnosed with NASH compared to healthy controls. Also, it has been reported that steatosis caused by NAFLD was associated with serum AGEs levels in a positive manner [ 44 ]. Also, a case-control study demonstrated that AGEs and their receptor (RAGE) are culprits in liver damage [ 45 ].…”