Higher hepatic advanced glycation end products and liver damage markers are associated with nonalcoholic steatohepatitis

• Published in: Nutrition research (New York, N.Y.) Vol. 104; pp. 71 - 81
• Main Authors: Priken, Kathleen, Tapia, Gladys, Cadagan, Cynthia, Quezada, Nicolás, Torres, Javiera, D'Espessailles, Amanda, Pettinelli, Paulina
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2022
• Subjects: Advanced glycation end products; Alpha-smooth muscle actin; Immunohistochemistry; Non-alcoholic fatty liver disease; Transforming growth factor beta1; Immunohistochemistry; SS; Transforming growth factor beta1; NAS; NAFLD; CML; DAB; Alpha-smooth muscle actin; AGEs; RAGE; NASH; α-SMA; HOMA-IR; NF-κB; Advanced glycation end products; TGF-β1; sRAGE; Non-alcoholic fatty liver disease; AUP; HbA1c; BMI
• ISSN: 0271-5317; 1879-0739
• DOI: 10.1016/j.nutres.2022.04.005

Advanced glycation end products (AGEs) may be associated with nonalcoholic fatty liver disease (NAFLD) from stimulation of oxidative stress, inflammation, and fibrosis. We hypothesized that patients with NAFLD would have a lower concentration of soluble AGEs receptor and higher quantity of serum and liver AGEs and an increase in hepatic smooth muscle actin alpha (α-SMA) and transforming growth factor beta 1 (TGF-β1) compared with a control group. We compared the presence of hepatic and serum AGEs, AGE soluble receptor (sRAGE), and markers associated with hepatic damage between NAFLD patients and controls without disease. Histological characteristics, plasma biochemical parameters, serum AGEs, serum receptor sRAGE, and liver proteins (α-SMA, TGF-β1, AGEs, immunohistochemistry) were assessed in participants aged 18 to 65 years, with NAFLD (simple steatosis [SS]: n = 7; steatohepatitis [NASH]: n = 15) and controls (n = 11). NASH patients presented higher glycated hemoglobin levels (%) (5.7; 5.4-6.3) compared with SS (5.4; 5.2-5.7) and controls (5.4; 5.3-5.5). The NAFLD activity score (NAS) for NASH patients was 4.9 ± 1.3; for SS patients, 2.0 ± 1.0. NASH patients showed higher hepatic AGEs, TGF-β1, and α-SMA compared with SS and control groups. The NAS score indicates that patients with 5 to 8 had higher hepatic AGEs, TGF-β1, and α-SMA compared with a NAS of 1 to 4 and 0. For α-SMA, a NAS of 1 to 4 was higher than NAS 0. No difference was found in serum AGEs and sRAGE between groups. Higher hepatic AGEs, TGF-β1, and α-SMA were observed with increasing disease severity (according to NAS); therefore, endogenous liver AGEs may participate in hepatic damage progression. [Display omitted]