Abstract
Previously, we reported that inverse associations of high-density lipoprotein (HDL) with cardiovascular disease and diabetes were only observed for HDL that lacked the pro-inflammatory protein apolipoprotein C3 (apoC3). To provide further insight into the cardiometabolic properties of HDL subspecies defined by the presence or absence of apoC3, we aimed to examine these subspecies with liver fat content and non-alcoholic fatty liver disease (NAFLD). We investigated cross-sectional associations between ELISA-measured plasma levels of apoA1 in HDL that contained or lacked apoC3 and computed tomography-determined liver fat content and NAFLD (<51 HU) at baseline (2000–2002) among 5007 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) without heavy alcohol consumption (>14 drinks/week in men and >7 drinks/week in women). In multivariable-adjusted regression models, apoA1 in HDL that contained or lacked apoC3 was differentially associated with liver fat content (Pheterogeneity = 0.048). While apoA1 in HDL that lacked apoC3 was inversely associated with liver fat content (Ptrend < 0.0001), apoA1 in HDL that contained apoC3 was not statistically significantly associated with liver fat content (Ptrend = 0.57). Higher apoA1 in HDL that lacked apoC3 was related to a lower prevalence of NAFLD (OR per SD: 0.80; 95% CI: 0.72, 0.89), whereas no association was found for apoA1 in HDL that contained apoC3 (OR per SD: 0.95; 95% CI: 0.85, 1.05; Pheterogeneity = 0.09). Higher apoA1 in HDL that lacked apoC3 was associated with less liver fat content and a lower prevalence of NAFLD. This finding extends the inverse association of HDL lacking apoC3 from cardiovascular disease to NAFLD. Lack of biopsy-proven hepatic steatosis and fibrosis data requires the replication of our study in further studies.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation in the absence of heavy alcohol intake
NAFLD frequently occurs in conjunction with obesity, insulin resistance, and dyslipidemia, conditions encompassed in the definition of the metabolic syndrome (MetS)
Based upon these previous findings on diabetes and coronary heart disease risk, two conditions strongly linked to NAFLD [9,11], we examined the association of apoA1 in high-density lipoprotein (HDL) that contained or lacked apolipoprotein C3 (apoC3) with liver fat content and NAFLD in the Multi-Ethnic Study of Atherosclerosis (MESA)
Summary
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive hepatic fat accumulation in the absence of heavy alcohol intake. Patients with MetS show increased catabolism of high-density lipoprotein (HDL), leading to decreased HDL cholesterol levels. Lower HDL cholesterol is commonly present in NAFLD. Accumulating evidence suggests that the physiological roles of HDL depend on its protein cargo. One of the most abundant proteins in HDL, beyond apoA1, is apolipoprotein C3 (apoC3), a pro-inflammatory glycoprotein primarily synthesized in the liver [5]. Previous research has suggested that polymorphisms in the APOC3 gene encoding the apoC3 protein might be responsible for genetic susceptibility to NAFLD [6]. ApoC3 has the potential to regulate liver fat accumulation by influencing circulating triglycerides
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