Fatty Liver Is Independently Associated With Alterations in Circulating HDL2 and HDL3 Subfractions

Abstract

Fatty liver is associated with insulin resistance, atherosclerosis, and the metabolic syndrome (1–7) and predicts future cardiovascular events (4–8). The pro-atherogenic serum lipid profile in subjects with fatty liver is characterized by elevated levels of triglycerides, low HDL cholesterol, and an increase in small dense LDL particles (9–12). Regarding HDL, not only quantitative, but also qualitative and compositional alterations are related to its antiatherogenic properties (13–16). In particular, circulating HDL2 was found to protect from atherosclerosis (17,18). In the present study, we first investigated whether fatty liver is associated with altered circulating HDL cholesterol subfractions and second whether this relationship is independent of insulin sensitivity, thus possibly representing a direct link between fatty liver and cardiovascular disease. In our ongoing study on the pathophysiology of type 2 diabetes, ∼300 Caucasians were carefully characterized for fatty liver and its associated metabolic characteristics (19). To select a subgroup that was representative for the percentage of subjects having fatty liver (liver fat >5.56%) (20) in our large cohort (∼40%) and in whom enough sample volume was available to measure the HDL cholesterol subfractions, we randomly selected 8 men and 8 women with fatty liver and 24 control subjects. The subjects underwent a 75-g oral glucose tolerance test to exclude diabetes and calculate insulin sensitivity (21). Total body fat was measured by bioelectrical impedance, visceral fat by magnetic resonance (MR) tomography, and liver fat by 1H-MR spectroscopy (19). Serum total, HDL, and LDL cholesterol, as well as triglyceride concentrations, were measured by standard colorimetry, plasma adiponectin …