Article

Serum Adipocyte Fatty Acid-Binding Protein Is Associated Independently with Vascular Inflammation: Analysis with F-18-Fluorodeoxyglucose Positron Emission Tomography

Department of Internal Medicine, Korea University, Sŏul, Seoul, South Korea
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 03/2011; 96(3):E488-92. DOI: 10.1210/jc.2010-1473
Source: PubMed

ABSTRACT The inflammatory status of atherosclerotic lesions is a major factor triggering acute cardiovascular events. Growing evidence has shown that adipocyte fatty acid-binding protein (A-FABP) has an important role in the development of atherosclerosis.
The objective of the study was to determine the association between circulating A-FABP levels with vascular inflammation as measured using [(18)F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), which is a novel imaging technique for noninvasive measurement of atherosclerotic inflammation.
This was a cross-sectional study.
Eighty-seven men without previously diagnosed cardiovascular disease or diabetes participated in the study.
We measured the serum A-FABP, adiponectin, and leptin levels as well as other cardiovascular risk factors. Vascular inflammation in the carotid arterial wall, as indicated by the target to background ratio (TBR), was analyzed using FDG-PET.
The circulating A-FABP and leptin levels had positive correlations with maximum TBR values (r = 0.38, P < 0.001; and r = 0.28, P = 0.010, respectively), whereas the adiponectin levels had a negative correlation (r = -0.31, P = 0.004). The maximum TBR levels exhibited an additive linear increment according to the rise in tertiles of the A-FABP levels in subjects with and without metabolic syndrome. Multiple regression analysis showed that serum A-FABP levels were independently associated with maximum TBR after adjustment for other cardiovascular risk factors (P = 0.006).
Circulating A-FABP, adiponectin, and leptin levels were shown to be associated with vascular inflammation, as measured using FDG-PET. Specifically, the A-FABP level was an independent risk factor for vascular inflammation in Korean men without cardiovascular disease or diabetes.

1 Follower
 · 
127 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Adipose fatty acid binding protein, aP2 (FABP4), contributes to the pathogenesis of several common diseases including type 2 diabetes, atherosclerosis, fatty liver disease, asthma, and cancer. Although the biological functions of aP2 have classically been attributed to its intracellular action, recent studies demonstrated that aP2 acts as an adipokine to regulate systemic metabolism. However, the mechanism and regulation of aP2 secretion remain unknown. Here, we demonstrate a specific role for lipase activity in aP2 secretion from adipocytes in vitro and ex vivo. Our results show that chemical inhibition of lipase activity and genetic deficiency of adipose triglyceride lipase (ATGL), and to a lesser extent, hormone-sensitive lipase (HSL) blocked aP2 secretion from adipocytes. Increased lipolysis and lipid availability also contributed to aP2 release as determined in perilipin1-deficient adipose tissue explants ex vivo and upon treatment with lipids in vivo and in vitro. In addition, we identify a non-classical route for aP2 secretion in exosome-like vesicles, and show that aP2 is recruited to this pathway upon stimulation of lipolysis. Given the effect of circulating aP2 on glucose metabolism, these data argue that targeting aP2 or the lipolysis dependent secretory pathway may present novel mechanistic and translational opportunities in metabolic disease. Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
    The Journal of Lipid Research 12/2014; 56(2). DOI:10.1194/jlr.M055798 · 4.73 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The traditional perception of adipose tissue as a storage organ of fatty acids has been replaced by the notion that adipose tissue is an active endocrine organ, releasing various adipokines that are involved in the pathogenesis of obesity-related metabolic disturbances. Obesity is a well-known risk factor for atherosclerosis, and accelerates atherosclerosis by many mechanisms such as increase in blood pressure and glucose level, abnormal lipid profiles, and systemic inflammation. Furthermore, growing evidence suggests that some adipokines directly mediate the process of atherosclerosis by influencing the function of endothelial cells, arterial smooth muscle cells, and macrophages in vessel walls. In obese patients, the secretion and coordination of such adipokines is abnormal, and the secretion of specific adipokines increases or decreases. Accordingly, the discovery of new adipokines and elucidation of their functions might lead to a new treatment strategy for metabolic disorders related to obesity, including cardiovascular diseases.
    06/2014; 5(3):357-363. DOI:10.4239/wjd.v5.i3.357
  • [Show abstract] [Hide abstract]
    ABSTRACT: We hypothesized that serum lipids, which experimental data suggest may be key initiators of carotid plaque inflammation, would be associated with plaque inflammation on (18)fluorodeoxyglucose (FDG)-PET in patients with acutely symptomatic carotid stenosis. In this cohort study, consecutive patients with acute symptomatic internal carotid artery (ICA) stenosis (≥50%) underwent carotid PET-CT. We quantified plaque FDG uptake as follows: (1) average maximum standardized uptake values (SUVmax) across 10 regions of interest (ROI); (2) highest single ROI SUV measure (SUVROImax); (3) averaged mean SUV across 10 ROIs (SUVmean). Sixty-one patients were included. Plaque inflammatory FDG SUVmax was associated with increasing tertiles of low-density lipoprotein (LDL) (trend p = 0.004), total cholesterol (p = 0.009), and triglycerides (p = 0.01), and with lower high-density lipoprotein (HDL) (p = 0.005). When analyzed as a continuous variable, LDL was associated with symptomatic ICA SUVmean (Spearman rho 0.44, p = 0.009), SUVROImax (rho 0.33, p = 0.01), and SUVmax (rho 0.35, p = 0.06). Total cholesterol was associated with SUVmean (rho 0.33, p = 0.009), with trends for SUVmax (rho 0.24, p = 0.059) and SUVROImax (rho 0.23, p = 0.08). Triglycerides were associated with SUVmax (rho 0.32, p = 0.01) and SUVROImax (rho 0.35, p = 0.005). HDL was associated with lower SUVmax (rho -0.37, p = 0.004) and SUVROImax (rho -0.44, p = 0.0004). On multivariable linear regression analysis adjusting for age, sex, degree of carotid stenosis, statins, and smoking, LDL (p = 0.008) and total cholesterol (p = 0.04) were independently associated with SUVmax. Serum LDL and total cholesterol were associated with acutely symptomatic carotid plaque FDG uptake, supporting experimental data suggesting lipids may promote plaque inflammation, mediating rupture and clinical events.
    Neurology 04/2014; 82(19). DOI:10.1212/WNL.0000000000000408 · 8.30 Impact Factor