1. Adiponectin Correlation With Plasma Lipoprotein Subclasses Determined By NMR And With The Risk Of Venous Thrombosis.
Fernández JA, Deguchi H, Pecheniuk NM, Elias DJ, Griffin JH.
The Scripps Research Institute, La Jolla, California, USA.
Introduction:
Adiponectin is a homotrimeric hormone derived from adipose tissue and its deficiency is linked to insulin resistance, coronary heart disease and dyslipidemia. The crystal structure of adiponectin showed its similarity to TNF-alpha that might be related to its anti-inflammatory properties. The physiologic roles of adiponectin are poorly understood. Recent reports suggest venous thrombosis is linked to dyslipoproteinemia (See poster 2379). To investigate the relationship of adiponectin levels with different lipoprotein subclasses that were quantitated in plasma by NMR, as well as the association of adiponectin levels with venous thrombosis, we measured adiponectin levels (by ELISA) for subjects in the Scripps VTE Registry (N=189), a well characterized age and sex matched venous thrombosis and control population.
Spearman Correlation of adiponectin with lipid parameters
r value
P value
Triglycerides
-0.45
<0.0001
LDL Cholesterol
-0.07
0.330
HDL cholesterol
0.40
Total cholesterol
-0.05
0.520
Apo B
-0.24
0.0013
Apo A1
0.22
0.0029
Age
-0.15
0.04
Gender
-0.27
0.0003
BMI kg/m2
-0.33
NMR TG (mg/dl)
-0.40
VLDL particle size
-0.32
VLDL Size
-0.09
0.223
Large VLDL
-0.37
Medium VLDL
-0.35
Small VLDL
-0.21
0.0049
VLDL TG Mass
-0.42
LDL particle size
LDL Size
0.44
IDL
0.054
Large LDL
0.30
Medium/small LDL
-0.44
►Small LDL
►Very small LDL
HDL particle total
0.08
0.3131
HDL size
0.45
Large HDL
Medium HDL
0.09
0.2498
Small HDL
<0.0003
HDL Chol Mass
0.36
There are no differences (P=0.5) in total adiponectin levels between VTE patients (7.7  0.4 μg/ml) and controls (7.3  0.3 μg/ml).
Scheme of Adiponectin ELISA protocol from Otsuka Pharmaceuticals, Japan. The intra-and inter-assay coefficients of variations were 3.3% and 7.4%, respectively.
No differences were seen between patients and controls when samples were divided by gender. Although the levels of adiponectin were higher in females (8.75 vs 6.65 μg/ml, P=0.0006)
Red denotes positive correlations
Correlation results
Significant Spearman positive correlations for adiponectin with HDL cholesterol (r =0.404), Apo AI (r =0.225) and negative correlations with BMI (r =-0.327), triglycerides (r = ), and apo B (r = ) were found suggesting an association of adiponectin with a healthy lipid profile in agreement with literature. The NMR lipoprotein subclasses of HDL, LDL and VLDL were further divided by particle size in large, medium, and small particles. The results revealed that adiponectin significantly correlates positively with large HDL and LDL and negatively with small HDL and LDL. The correlation of adiponectin with each VLDL subclass was negative consistent with the known negative correlation with triglycerides. In summary, these results imply that the relationship of adiponectin with lipoproteins is more complex than previously estimated and is more related to large lipoprotein particle size, independent of the apolipoprotein content. In contrast to coronary heart disease, low adiponectin levels appear not to be related to venous thrombosis.
NMR lipoprotein subclass analysis
Lipoprotein particle concentrations of 10 lipoprotein subclasses in EDTA plasma were determined by proton NMR spectroscopy at LipoScience (Raleigh, NC). The subclass categories based on particle diameter range comprised: 3 VLDL subpopulations [chylomicron/large VLDL, intermediate VLDL, and small VLDL]; 3 LDL subpopulations [IDL, large LDL, and small LDL which was also reported as medium small LDL and very small LDL]; and 3 HDL subpopulations [large HDL, medium HDL and small HDL]. Values for mean VLDL, LDL, and HDL particle size were also calculated. The NMR-derived lipoprotein particle levels are based on the NMR signals that are characteristic of typical lipoprotein particles and are not actual lipid measurements. NMR data are directly proportional to the number of particles, independent of lipid or apolipoprotein per particle which may vary from person to person.
A typical plasma NMR spectrum is shown, highlighting the spectral region at ~0.8 ppm containing the information used to derive the subclass concentrations. This region contains the signals emitted by the methyl group protons of the four types of lipid in the particles: phospholipid, cholesterol, cholesterol ester, and triglyceride. Since the methyl signals from these lipids are indistinguishable from each other, they overlap to produce a bulk lipid “particle signal”. The amplitude of each lipoprotein particle signal serves as a measure of the concentration of that lipoprotein. What makes it possible to exploit the methyl lipid signal for lipoprotein subclass quantification is a magnetic property specific to lipoproteins that causes the lipids in larger particles to broadcast signals that are characteristically different in frequency and shape from the lipid signals emitted by smaller particles (reprinted from LipoScience.com).
Conclusions
1) In contrast to arterial atherothrombosis, total adiponectin levels are not a marker for venous thrombosis.
2) Adiponectin levels correlate positively with a good lipid profile and negatively with a bad lipid profile.
3) Adiponectin levels correlate with larger lipoprotein particle size independent of apolipoprotein content.