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 HDL 2 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.RESEARCH DESIGN AND METHODS -In our ongoing study on the pathophysiology of type 2 diabetes, ϳ300 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 Ͼ5.56%) (20) in our large cohort (ϳ40%) 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 1 H-MR spectroscopy (19). Serum total, HDL, and LDL cholesterol, as well as triglyceride concentrations, were measured by standard colorimetry, plasma adiponectin by radioimmunoassay, and apolipoprotein (apo)B 100 and apoA-I by immunonephelometry. Circulating HDL 2 and HDL 3 cholesterol levels were quantified after ultracentrifugation of 1.5 ml serum (22), and the fatty acid pattern of these subfractions was determined by gas chromatography (23) within the entire particle, thereafter, in a subgroup of 34 subjects in whom sufficient sample volume was available after ultracentrifugation and chemical derivatization. A total of 15 subjects had fatty liver, and 19 were control subjects. Intima-media thickness (IMT) of the carotid artery was measured by high-resolution ultrasound. Relationships between parameters were tested using univariate correlations, and multivariate linear regression models were used to investigate independent relationships. P Յ 0.05 was considered statistically significant.RESULTS -Altogether, 25 women and 15 men were studied. While age (P ϭ 0.08) and total body fat (P ϭ 0.23) were not different between subjects with fatty liver and control subjects, individuals with fatty liver had higher body weight (P ϭ 0.02), BMI (P ϭ 0.002), waist circumference (P ϭ 0.003), and visceral fat (P Ͻ 0.0001), as well as higher IMT (P ϭ 0.04). Furthermore, they had higher fasting (P ϭ 0.006) and 2-h (P ϭ 0...

High-density lipoprotein subspecies between patients with type 1 diabetes and type 2 diabetes without / with intensive insulin therapy

“…Our literature review on HDL-C subspecies indicated that HDL3-C levels are much higher than HDL2-C levels in non-diabetic populations [6,11], and that HDL2-C levels are substantially reduced in diabetic populations [6,9] in Western countries. The relatively low ratio of HDL2-C to HDL3-C might explain the higher incidence of CHD in Western populations compared to that in the Japanese population.…”

“…In Western populations, in contrast, HDL3-C is usually higher than HDL2-C [6,11]. This conspicuous difference in the composition of HDL subspecies between Japanese and Western populations underlines the importance of examining HDL subspecies in Japanese patients with T1D and T2D.…”

Environmental and Genetic Determinants of Fatty Liver in Humans

“…Metabolic consequences of fatty liver are hyperglycemia, dyslipidemia and subclinical inflammation, which is accompanied by hepatic insulin resistance ( fig. 1 ) [50,65,[121][122][123] . It is thought that peripheral insulin resistance is a cause of fat accumulation in the liver.…”

Dissociation Between Fatty Liver and Insulin Resistance in Humans Carrying a Variant of the Patatin-Like Phospholipase 3 Gene

“…It constitutes a major risk factor for progression to liver failure, cirrhosis, and hepatocellular carcinoma (1,2). In addition, NAFLD is strongly associated with insulin resistance and atherosclerosis, independently of other risk factors such as total and visceral adiposity (3–14). Moreover, NAFLD is becoming increasingly recognized as a condition strongly involved in the pathogenesis of the epidemically spreading metabolic diseases type 2 diabetes and cardiovascular disease (10,11).…”

“…Metabolic consequences of fatty liver are hyperglycemia, dyslipidemia, and subclinical inflammation (12–14). As an underlying hepatic molecular mechanism, fatty acids in the liver promote a hepatic inflammatory response, which is referred to as lipotoxicity or nonalcoholic steatohepatitis (NASH).…”