Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis.
OBJECTIVE
Advanced glycation end products (AGE), senescent macroprotein derivatives formed at an accelerated rate in diabetes, play important roles in the pathogenesis of diabetic vascular complications. Recently, AGE have also been found to be involved in insulin resistance. Although non-alcoholic steatohepatitis (NASH) is generally considered a hepatic manifestation of insulin resistance, there are no reports showing the link of AGE to NASH. The aim of this study was to evaluate the clinical significance of AGE in patients with NASH.


METHODS
Glyceraldehyde-derived AGE levels were assayed from serum obtained from 106 patients: 66 with NASH, 10 with simple steatosis, and 30 controls.


RESULTS
Serum glyceraldehyde-derived AGE levels (U/mL) were significantly elevated in NASH patients (9.78 +/- 3.73) compared with simple steatosis (7.17 +/- 2.28, P = 0.018) or healthy controls (6.96 +/- 2.36, P = 0.003). Moreover, these were inversely correlated with adiponectin, an adipocytokine with insulin-sensitizing and anti-inflammatory properties. In addition, immunohistochemistry of glyceraldehyde-derived AGE showed intense staining in the livers of NASH patients.


CONCLUSIONS
The present data suggest that the sustained increase of glyceraldehyde-derived AGE could at least in part contribute to the pathogenesis of NASH. The serum glyceraldehyde-derived AGE level may be a useful biomarker for discriminating NASH from simple steatosis.
Hyogo
Hideyuki
H
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Yamagishi
Sho-ichi
S
Iwamoto
Keiko
K
Arihiro
Koji
K
Takeuchi
Masayoshi
M
Sato
Takashi
T
Ochi
Hidenori
H
Nonaka
Michihiro
M
Nabeshima
Yoshitaka
Y
Inoue
Motoki
M
Ishitobi
Tomokazu
T
Chayama
Kazuaki
K
Tazuma
Susumu
S
D000328:Adult; D000368:Aged; D005234:Fatty Liver / Q000097:blood* / Q000150:complications; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006505:Hepatitis / Q000097:blood* / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged
D017127:Glycation End Products, Advanced