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

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.

The hepatokine Tsukushi is released in response to NAFLD and impacts cholesterol homeostasis

“…Alterations in circulating HDL subfractions have also been detected in patients with NAFLD (60). In line with these findings, reduced cholesterol efflux capacity was detected in plasma from humans with NAFLD (59,63). Such reduction in cholesterol efflux was proposed as a possible mechanism linking NAFLD to cardiovascular diseases (59,63).…”

“…In line with these findings, reduced cholesterol efflux capacity was detected in plasma from humans with NAFLD (59,63). Such reduction in cholesterol efflux was proposed as a possible mechanism linking NAFLD to cardiovascular diseases (59,63). How exactly NAFLD affects HDLs to reduce reverse cholesterol transport and promote cardiovascular risk is still elusive.…”

“…NAFLD is associated with insulin resistance and atherosclerosis and predicts cardiovascular events in humans (53)(54)(55)(56)(57)(58). Atherogenic alterations in lipoprotein subclasses are found in NAFLD, including increased small and dense LDL particles, low HDL cholesterol, low ApoA1, and elevated triglycerides (59)(60)(61)(62). Alterations in circulating HDL subfractions have also been detected in patients with NAFLD (60).…”

High‐fat diet aggravates the liver disease caused by periodontitis in rats

“…In our study, concentrations of total cholesterol from the group with periodontitis and high‐fat diet were high in comparison with the control and the periodontitis groups. In addition, HDL cholesterol also presented significantly changed values, the lowest ones, only in the high‐fat group, corroborating the studies in which steatosis was frequently related to its low levels . HDL is a lipoprotein with heterogeneous density and it is diminished considering the dyslipidemia present in this case .…”

Non-alcoholic fatty liver disease and cardiovascular disease: A still debated liaison

“…HDL CEC was suppressed in NAFLD patients, suggesting that impaired HDL functions may be an independent risk factor for atherosclerosis in NAFLD. 11 Hepatic fat content and the progression of liver damage have a strong heritable component. The common variants I148M in the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) and E167K in the Transmembrane 6 superfamily member 2 (TM6SF2) genes predispose to NAFLD and advanced liver disease but protect against CVD.…”