Serum adiponectin level is correlated with the size of HDL and LDL particles determined by high performance liquid chromatography



      Adiponectin (APN) improves insulin resistance and prevents atherosclerosis, and HDL removes cholesterol from atherosclerotic lesions. We have demonstrated that serum HDL-cholesterol (HDL-C) and APN concentrations are positively correlated and that APN accelerates reverse cholesterol transport (RCT) by increasing HDL synthesis in the liver and cholesterol efflux from macrophages. We previously reported that APN reduced apolipoprotein (apo) B secretion from the liver. It is well-known that insulin resistance influences the lipoprotein profile. In this study, we investigated the clinical significance of APN levels and insulin resistance in lipoprotein metabolism.


      We investigated the correlation between serum APN concentration, HOMA-R, the lipid concentrations and lipoprotein particle size by high-performance liquid chromatography (HPLC) in 245 Japanese men during an annual health checkup.


      Serum APN level was positively correlated with the cholesterol content in large LDL and HDL particles, but inversely correlated with the cholesterol content in large VLDL and small LDL particles. HOMA-R was negatively correlated with the cholesterol content in large LDL and HDL particles and positively correlated with the cholesterol content in large VLDL and small LDL particles. By multivariate analysis, APN was correlated with the particle size of LDL-C and HDL-C independently of age, BMI and HOMA-R.


      APN may be associated with the formation of both HDL and LDL particles, reflecting the enhancement of RCT and the improvement in TG-rich lipoprotein metabolism and insulin resistance.



      HDL-C (High Density Lipoprotein-Cholesterol), LDL-C (Low Density Lipoprotein-Cholesterol), VLDL-C (Very Low Density Lipoprotein-Cholesterol), HPLC (High Performance Liquid Chromatography), APN (Adiponectin), RCT (Reverse Cholesterol Transport), Apo (Apolipoprotein), CAD (Coronary Artery Disease), NMR (Nuclear Magnetic Resonance)
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        • Rizzo M.
        • Berneis K.
        • Corrado E.
        • et al.
        The significance of low-density-lipoproteins size in vascular diseases.
        Int Angiol. 2006; 25: 4-9
        • Miller N.E.
        • La Ville A.
        • Crook D.
        Direct evidence that reverse cholesterol transport is mediated by high density lipoprotein in rabbit.
        Nature. 1985; 314: 109-111
        • Maeda K.
        • Okubo K.
        • Shimomura I.
        • et al.
        cDNA cloning and expression of a novel adipose specific collagen-like factor, aPM1 (adipose most abundant gene transcript 1).
        Biochem Biophys Res Commun. 1996; 221: 286-289
        • Scherer P.E.
        • Williams S.
        • Fogliano M.
        • et al.
        A novel serum protein similar to C1q, produced exclusively in adipocytes.
        J Biol Chem. 1995; 270: 26746-26749
        • Ouchi N.
        • Kihara S.
        • Arita Y.
        • et al.
        Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin.
        Circulation. 1999; 100: 2473-2476
        • Kazumi T.
        • Kawaguchi A.
        • Sakai K.
        • et al.
        Young men with high-normal blood pressure have lower serum adiponectin, smaller LDL size, and higher elevated heart rate than those with optimal blood pressure.
        Diabetes Care. 2002; 25: 971-976
        • Mallamaci F.
        • Zoccali C.
        • Cuzzola F.
        • et al.
        Adiponectin in essential hypertension.
        J Nephrol. 2002; 15: 507-511
        • Engeli S.
        • Feldpausch M.
        • Gorzelniak K.
        • et al.
        Association between adiponectin and mediators of inflammation in obese women.
        Diabetes. 2003; 289: 1799-1804
        • Ouchi N.
        • Kihara S.
        • Funahashi T.
        • et al.
        Obesity, adiponectin and vascular inflammatory disease.
        Curr Opin Lipidol. 2003; 14: 561-566
        • Miyoshi Y.
        • Funahashi T.
        • Kihara S.
        • et al.
        Association of serum adiponectin levels with breast cancer risk.
        Clin Cancer Res. 2003; 9: 5699-5704
        • Ryo M.
        • Nakamura T.
        • Kihara S.
        • et al.
        Adiponectin as a biomarker of the metabolic syndrome.
        Circ J. 2004; 68: 975-981
        • Matsuura F.
        • Oku H.
        • Koseki M.
        • et al.
        Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver.
        Biochem Biophys Res Commun. 2007; 358: 1091-1095
        • Oku H.
        • Matsuura F.
        • Koseki M.
        • et al.
        Adiponectin deficiency suppresses ABCA1 expression and apo A-I synthesis in the liver.
        FEBS Lett. 2007; 581: 5029-5033
        • Tsubakio-Yamamoto K.
        • Matsuura F.
        • Koseki M.
        • et al.
        Adiponectin prevents atherosclerosis by increasing cholesterol efflux from macrophages.
        Biochem Biophys Res Commun. 2008; 375: 390-394
        • Lautamäki R.
        • Rönnemaa T.
        • Huupponen R.
        • et al.
        Low serum adiponectin is correlated with high circulating oxidized low-density lipoprotein in patients with type 2 diabetes mellitus and coronary artery disease.
        Metabolism. 2007; 56: 881-886
        • Giannessi D.
        • Caselli C.
        • Ry S.D.
        • et al.
        Adiponectin is associated with abnormal lipid profile and coronary microvascular dysfunction in patients with dilated cardiomyopathy without overt heart failure.
        Metabolism. 2011; 60: 227-233
        • Blüher M.
        • Fasshauer M.
        • Klöting N.
        • et al.
        Gene expression of adiponectin receptors in human visceral and subcutaneous adipose tissue is related to insulin resistance and metabolic parameters and is altered in response to physical training.
        Diabetes Care. 2007; 30: 3110-3115
        • Matsunami T.
        • Sato Y.
        • Ariga S.
        • et al.
        Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model.
        Metabolism. 2011; 60: 805-814
        • Howard Barbara V.
        • Mayer-Davis Elizabeth J.
        • Goff David
        • et al.
        Relationships between insulin resistance and lipoproteins in nondiabetic Africans, Hispanics, and non-Hispanic whites: the Insulin Resistance Atherosclerosis Study.
        Metabolism. 1998; 47: 1174-1179
        • Garvey W.T.
        • Kwon S.
        • Zheng D.
        • et al.
        Effects of insulin resistance and type 2 diabetes on lipoprotein subclass particle size and concentration determined by nuclear magnetic resonance.
        Diabetes. 2003; 53: 453-462
        • Sam S.
        • Haffner S.
        • Davidson M.H.
        • et al.
        Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes.
        Diabetes. 2008; 57: 2022-2027
        • Festa A.
        • Williams K.
        • Hanley A.J.
        • et al.
        Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the Insulin Resistance Atherosclerosis Study.
        Circulation. 2005; 111: 3465-3472
        • Goff Jr., D.C.
        • D'Agostino Jr., R.B.
        • Haffner S.M.
        • et al.
        Insulin resistance and adiposity influence lipoprotein size and subclass concentrations. Results from the Insulin Resistance Atherosclerosis Study.
        Metabolism. 2005; 54: 264-270
        • Arita Y.
        • Kihara S.
        • Ouchi N.
        • et al.
        Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity.
        Biochem Biophys Res Commun. 1999; 257: 79-83
        • Masuda D.
        • Nakagawa-Toyama Y.
        • Nakatani K.
        • et al.
        Ezetimibe improves postprandial hyperlidaemia in patients with type IIB hyperlipidaemia.
        Eur J Clin Invest. 2009; 39: 689-698
        • Okazaki M.
        • Usui S.
        • Hosaki S.
        Analysis of plasma lipoproteins by gel permeation chromatography.
        in: Rifai N. Warnick G.R. Dominiczak M.H. Handbook of lipoprotein testing. AACC Press, Washington, DC2000: 647-669
        • Usui S.
        • Nakamura M.
        • Jitsukata K.
        • et al.
        Assessment of between-instrument variations in an HPLC method for serum lipoproteins on high performance liquid chromatography.
        J Biochem. 1982; 92: 517-524
        • Matsuzawa Y.
        Metabolic syndrome—definition and diagnostic criteria in Japan.
        J Atheroscler Thromb. 2005; 12: 301
        • Okazaki M.
        • Usui S.
        • Ishigami M.
        • et al.
        Identification of unique lipoprotein subclasses for visceral obesity by component analysis of cholesterol profiles in high-performance liquid chromatography.
        Arterioscler Thromb Vasc Biol. 2005; 25: 578-584
        • Kobayashi H.
        • Nakamura T.
        • Miyaoka K.
        • et al.
        Visceral fat accumulation contributes to insulin resistance, small sized low-density lipoprotein, and progression of coronary artery disease in middle-aged non-obese Japanese men.
        Jpn Circ J. 2001; 65: 193-199
        • Ruan H.
        • Harvey F.
        • et al.
        Insulin resistance in adipose tissue: direct and indirect effects of tumor necrosis factor-alpha.
        Cytokine Growth Factor Rev. 2003; 14: 447-455
        • Shetty G.K.
        • Mantzoros C.S.
        • Economides P.A.
        • et al.
        Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes.
        Diabetes Care. 2004; 27: 2450-2457
        • Makgos F.
        • Fabbrini E.
        • Patterson B.W.
        • et al.
        Portal vein and systemic adiponectin concentrations are closely linked with hepatic glucose and lipoprotein kinetics in extremely obese subjects.
        Metabolism. 2011; 60: 1641-1648
        • Chan D.C.
        • Watts G.F.
        • Ooi E.M.M.
        • et al.
        Apolipoprotein A-II and adiponectin as determinants of very low-density lipoprotein apolipoprotein B-100 metabolism in nonobese men.
        Metabolism. 2011; 60: 1482-1487
        • Mantzoros C.S.
        • Li T.
        • Manson J.E.
        • et al.
        Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in woman with type 2 diabetes.
        J Clin Endocrinol Metab. 2005; 90: 4542-4548
        • Addy C.L.
        • Gavrila A.
        • Tsiodras S.
        • et al.
        Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy.
        J Clin Endocrinol Metab. 2003; 88: 627-636
        • Magkos F.
        • Mantzoros C.S.
        Body fat redistribution and metabolic abnormalities in HIV-infected patients on highly active antiretroviral therapy: novel insights into pathophysiology and emerging opportunities for treatment.
        Metabolism. 2011; 60: 749-753
        • Brown A.
        • Baker P.W.
        • Gibbons G.F.
        Changes in fatty acid metabolism in rat hepatocytes in response to dietary n-3 fatty acids are associated with changes in the intracellular metabolism and secretion of apolipoprotein B-48.
        J Lipid Res. 1997; 38: 469-481
        • Weiss R.
        • Otvos J.D.
        • Flyvbjerg A.
        • et al.
        Adiponectin and lipoprotein particle size.
        Diabetes Care. 2009; 32: 1317-1319
        • Li Z.
        • Otvos J.D.
        • Lamon-Fava S.
        • et al.
        Men and women differ in lipoprotein response to dietary saturated fat and cholesterol restriction.
        J Nutr. 2003; 133: 3428-3433