The endothelial function biomarker soluble E‐selectin is associated with nonalcoholic fatty liver disease

Abstract

Abbreviations: AFLD, alcoholic fatty liver disease; CODAM, Cohort on Diabetes and Atherosclerosis Maastricht; CVD, cardiovascular disease; GCKR, glucokinase regulatory protein; IGM, impaired glucose metabolism; NAFLD, nonalcoholic fatty liver disease; NAS, NAFLD activity score; NASH, nonalcoholic steatohepatitis; NGM, normal glucose metabolism; PNPLA3, patatin-like phospholipase domain-containing protein 3; sE-selectin, soluble E-selectin; sVCAM-1, soluble vascular cell adhesion molecule-1; T2DM, type 2 diabetes; VAT, visceral adipose tissue. AbstractBackground & Aims: Plasma soluble E-selectin (sE-selectin) is a frequently used biomarker of systemic endothelial dysfunction. The present study explored the relationship between nonalcoholic fatty liver disease (NAFLD) and plasma sE-selectin levels. Methods:Expression of E-selectin in liver, visceral adipose tissue (VAT) and muscle was studied in relation to plasma sE-selectin in severely obese individuals (n = 74).The course of hepatic E-selectin expression in relation to hepatic steatosis and inflammation was examined in C57BL/6J LDLR −/− mice on a Western-type diet. The relationship between biomarkers of NAFLD, that is, plasma aminotransferase (ALT) and

Genome-wide association study revealed novel candidate gene loci associated with soluble E-selectin levels in a Taiwanese population

“…We also found that parameters of liver function status, such as serum ALT, AST, and γGT levels were positively associated with sE-selectin levels in univariate and multivariate analyses, which is similar to those reported in Japanese men [30]. These results are also compatible with previous studies showing elevation of sE-selectin level and higher expression of hepatic E-selectin in patients with nonalcoholic fatty liver disease [31]. Mochizuki et al [30] have revealed a positive association between sE-selectin levels and leukocyte and neutrophil counts.…”

Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 Modulate Macrophage Gene Expression and Ameliorate Damage Markers in the Liver of Zucker-Leprfa/fa Rats

“…Specific adhesion glycoproteins are involved in the binding of leukocytes to endothelial cells [ 40 ]. NAFLD is associated with elevated circulating levels of E-selectin and sICAM [ 29 , 41 ]. We did not find differences in either E-selectin or hepatic LPS among the experimental groups, which suggests that changes in hepatic liver inflammation were not associated with changes in hepatic LPS.…”

E-Selectin-Dependent Inflammation and Lipolysis in Adipose Tissue Exacerbate Steatosis-to-NASH Progression via S100A8/9

“…E-selectin was documented previously to be implicated in inflammation of the liver 14 , 39 and adipose tissue. 40 Increased soluble E-selectin in plasma has been shown to be associated with NAFLD severity in patients.…”

“…It is known that adipose tissue likely has higher levels of FFAs than liver tissue, which probably contributes, at least in part, to the greater induction of E-selectin in adipose tissue when compared with liver tissue. E-selectin was documented previously to be implicated in inflammation of the liver 14,39 and adipose tissue. 40 Increased soluble E-selectin in plasma has been shown to be associated with NAFLD severity in patients.…”

“… 40 Increased soluble E-selectin in plasma has been shown to be associated with NAFLD severity in patients. 39 , 41 However, how E-selectin contributes to the NAFLD pathogenesis remains unknown. Now, we provide evidence supporting that this molecule indeed plays a specific regulating function during the steatosis-to-NASH transition.…”