"Non alcoholic fatty liver disease and eNOS dysfunction in humans"

Area of Science:

• Cardiovascular Research
• Hepatology
• Endocrinology

Background:

• Non-alcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance (IR), a condition known to impair endothelial nitric oxide synthase (eNOS) function and cause endothelial dysfunction (ED).
• While experimental models suggest eNOS dysfunction in NAFLD, direct evidence in human subjects has been lacking.
• This study aimed to investigate eNOS function in patients with NAFLD.

Purpose of the Study:

• To investigate endothelial nitric oxide synthase (eNOS) function in patients diagnosed with non-alcoholic fatty liver disease (NAFLD).
• To explore the association between NAFLD, insulin resistance, and endothelial dysfunction.
• To compare eNOS function in patients with simple fatty liver (NAFL) versus non-alcoholic steatohepatitis (NASH).

Main Methods:

• Fifty-four NAFLD patients were enrolled and categorized into NAFL and NASH groups based on liver biopsy.
• Vascular reactivity was assessed using isolated mouse aorta rings treated with patient platelets, alongside immunoblot assays for phosphorylated eNOS (p-eNOS) in platelets and liver tissue.
• Flow-mediated dilation (FMD) was measured, and all data were compared to healthy controls.

Main Results:

• NAFLD patients exhibited reduced platelet-induced vascular reactivity and impaired p-eNOS levels in both platelets and liver tissue compared to controls.
• Patients with simple fatty liver (NAFL) showed a greater impairment in eNOS phosphorylation than those with NASH.
• Flow-mediated dilation (FMD) results contrasted with in vitro findings, showing worse vascular response in NASH compared to NAFL.

Conclusions:

• This study provides the first human evidence of significant eNOS dysfunction in NAFLD patients.
• The observed eNOS dysfunction may contribute to an elevated cardiovascular risk in individuals with NAFLD.
• Discrepancies between in vitro eNOS function assessments and in vivo FMD measurements highlight the complexity of endothelial function in NAFLD.