Impaired HDL cholesterol efflux capacity in patients with non-alcoholic fatty liver disease is associated with subclinical atherosclerosis

Reza Fadaei,Reza Meshkani,Nariman Moradi,Hossein Poustchi,Shahin Merat,Taghi Golmohammadi

doi:10.1038/s41598-018-29639-5

Abstract

Non-alcoholic fatty liver disease (NAFLD) is associated with a substantial increased risk of atherosclerotic cardiovascular disease (ASCVD), which is partly related to dyslipidemia and low HDL-C level. The cardioprotective activity of HDL in the body is closely connected to its role in promoting cholesterol efflux, which is determined by cholesterol efflux capacity (CEC). Hitherto, the role of HDL, as defined by CEC has not been assessed in NAFLD patients. In this research study, we present the results of a study of cAMP-treated J774 CEC and THP-1 macrophage CEC in ApoB-depleted plasma of 55 newly diagnosed NAFLD patients and 30 controls. Circulating levels of ApoA-I, ApoB, preβ-HDL, plasma activity of CETP, PLTP, LCAT and carotid intima-media thickness (cIMT) were estimated. cAMP-treated J774 and THP-1 macrophage CEC were found to be significantly lower in NAFLD patients compared to controls (P < 0.001 and P = 0.003, respectively). In addition, it was discovered that both ApoA-I and preβ1-HDL were significantly lower in NAFLD patients (P < 0.001). Furthermore, cAMP-treated J774 CEC showed independent negative correlation with cIMT, as well as the presence of atherosclerotic plaque in NAFLD patients. In conclusion, our findings showed that HDL CEC was suppressed in NAFLD patients, and impaired cAMP-treated J774 CEC was an independent risk factor for subclinical atherosclerosis in NAFLD patients, suggesting that impaired HDL functions as an independent risk factor for atherosclerosis in NAFLD.

Highlights

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide, and includes a spectrum of liver disease conditions such as benign steatosis, inflammatory non-alcoholic steatohepatitis, fibrotic and cirrhotic liver disease conditions[1]
There was no significant difference in fasting blood glucose (FBG) between both groups
Patients with NAFLD demonstrated higher levels of triglycerides (TG) (P = 0.015) and lower levels of high-density lipoprotein cholesterol (HDL-C) (P = 0.025), and there was no significant difference in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) between both groups

Summary

Introduction

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease worldwide, and includes a spectrum of liver disease conditions such as benign steatosis, inflammatory non-alcoholic steatohepatitis, fibrotic and cirrhotic liver disease conditions[1]. Numerous studies have revealed that NAFLD is associated with increased risk of atherosclerosis cardiovascular disease (ASCVD)[2,3,4], which is the leading cause of death in NAFLD patients worldwide[5,6]. Low high-density lipoprotein cholesterol (HDL-C) level, which is associated with atherogenic dyslipidemia in NAFLD, is a known risk factor for ASCVD8,9. Recent studies have shown that HDL-C levels do not adequately predict ASCVD, and suggested that HDL function, in cholesterol efflux capacity (CEC) might better explain the risk associated with low HDL11,12. Several studies have shown atherogenic alterations in lipoprotein subclasses in relation to NAFLD15–17; until now there were no data on the relationship between CEC and subclinical atherosclerosis in NAFLD. The aim of this study was to evaluate the relationship between CEC and subclinical atherosclerosis in NAFLD patients and control subjects

Objectives

Methods

Results

Conclusion