Clinical Science| Volume 62, ISSUE 1, P109-120, January 2013

Download started.


Binding of adiponectin and C1q in human serum, and clinical significance of the measurement of C1q–adiponectin / total adiponectin ratio



      Adiponectin and C1q have similar sequences, exist abundantly in blood, and are produced by adipose tissues. The aim of this study was to examine whether adiponectin and C1q form protein-complex in blood and to know the clinical significance of the C1q–adiponectin (C1q–APN) complex in serum.


      The direct interaction between adiponectin and C1q was investigated by far western blotting and co-immunoprecipitation. The relationship between serum C1q–APN and various clinical features was analyzed in 329 Japanese men who underwent health check-up, including measurements of visceral (VFA) and subcutaneous fat area (SFA) by computed tomography (Victor-J study).


      Adiponectin bound to C1q in vitro and C1q–APN complex existed in human blood. C1q–APN complexes were identified in high- and middle-molecular weight forms of adiponectin in human serum by gel-filtration chromatography. Stepwise multiple regression analysis identified body mass index, VFA and SFA as significant determinants of serum C1q–APN level. Serum C1q–APN/Total-APN ratio correlated positively with cardiovascular risk factor accumulation in subjects with VFA ≥100 cm2.


      These results indicate that high- and middle-molecular forms of adiponectin partly consist of adiponectin-complex with other proteins including C1q and that the blood C1q–APN/Total-APN ratio may serve as a biomarker of the metabolic syndrome in general male subjects.


      C1q–APN (C1q-binding adiponectin), FWB (far western blotting), HMW (high-molecular weight), LMW (low-molecular weight), MMW (middle-molecular weight), HMW-APN (high molecular weight-adiponectin), rhAPN (recombinant human adiponectin), Total-APN (total-adiponectin)


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Metabolism - Clinical and Experimental
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • 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
        • Maeda K.
        • Okubo K.
        • Shimomura I.
        • et al.
        Analysis of an expression profile of genes in the human adipose tissue.
        Gene. 1997; 190: 227-235
        • 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
        • Hu E.
        • Liang P.
        • Spiegelman B.M.
        AdipoQ is a novel adipose-specific gene dysregulated in obesity.
        J Biol Chem. 1996; 271: 10697-10703
        • Nakano Y.
        • Tobe T.
        • Choi-Miura N.H.
        • et al.
        Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma.
        J Biochem. 1996; 120: 803-812
        • Okamoto Y.
        • Arita Y.
        • Nishida M.
        • et al.
        An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls.
        Horm Metab Res. 2000; 32: 47-50
        • 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
        • Matsuzawa Y.
        Adiponectin: a key player in obesity related disorders.
        Curr Pharm Des. 2010; 16: 1896-1901
        • Ouchi N.
        • Kihara S.
        • Arita Y.
        • Maeda K.
        • Kuriyama H.
        • Okamoto Y.
        • Hotta K.
        • Nishida M.
        • Takahashi M.
        • Nakamura T.
        • Yamashita S.
        • Funahashi T.
        • Matsuzawa Y.
        Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin.
        Circulation. 1999; 100: 2473-2476
        • Ryo M.
        • Nakamura T.
        • Kihara S.
        • et al.
        Adiponectin as a biomarker of the metabolic syndrome.
        Circ J. 2004; 68: 975-981
        • Pajvani U.B.
        • Du X.
        • Combs T.P.
        • et al.
        Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications for metabolic regulation and bioactivity.
        J Biol Chem. 2003; 278: 9073-9085
        • Arita Y.
        • Kihara S.
        • Ouchi N.
        • et al.
        Adipocyte-derived plasma protein adiponectin acts as a platelet-derived growth factor-BB-binding protein and regulates growth factor-induced common postreceptor signal in vascular smooth muscle cell.
        Circulation. 2002; 105: 2893-2898
        • Takemura Y.
        • Ouchi N.
        • Shibata R.
        • et al.
        Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies.
        J Clin Invest. 2007; 117: 375-386
        • Masaie H.
        • Oritani K.
        • Yokota T.
        • et al.
        Adiponectin binds to chemokines via the globular head and modulates interactions between chemokines and heparan sulfates.
        Exp Hematol. 2007; 35: 947-956
        • Komura N.
        • Kihara S.
        • Sonoda M.
        • et al.
        Increment and impairment of adiponectin in renal failure.
        Cardiovasc Res. 2010; 86: 471-477
        • Yokota T.
        • Oritani K.
        • Takahashi I.
        • et al.
        Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages.
        Blood. 2000; 96: 1723-1732
        • Ebina K.
        • Oshima K.
        • Matsuda M.
        • et al.
        Adenovirus-mediated gene transfer of adiponectin reduces the severity of collagen-induced arthritis in mice.
        Biochem Biophys Res Commun. 2009; 378: 186-191
        • Barbara D.J.
        • Clark M.F.
        A simple indirect ELISA using F(ab')2 fragments of immunoglobulin.
        J Gen Virol. 1982; 58: 315-322
        • Komura N.
        • Kihara S.
        • Sonoda M.
        • et al.
        • Osaka CAD Group
        Clinical significance of high-molecular weight form of adiponectin in male patients with coronary artery disease.
        Circ J. 2008; 72: 23-28
        • Teramoto T.
        • Sasaki J.
        • Ueshima H.
        • et al.
        Metabolic syndrome.
        J Atheroscler Thromb. 2008; 15: 1-5
        • Hughes-Jones N.C.
        • Gardner B.
        Reaction between the isolated globular sub-units of the complement component C1q and IgG-complexes.
        Mol Immunol. 1979; 16: 697-701
        • McGrath F.D.
        • Brouwer M.C.
        • Arlaud G.J.
        • et al.
        Evidence that complement protein C1q interacts with C-reactive protein through its globular head region.
        J Immunol. 2006; 176: 2950-2957
        • Dillon S.P.
        • D'Souza A.
        • Kurien B.T.
        • Scofield R.H.
        Systemic lupus erythematosus and C1q: a quantitative ELISA for determining C1q levels in serum.
        Biotechnol J. 2009; 4: 1210-1214
        • Horák P.
        • Hermanová Z.
        • Zadrazil J.
        • et al.
        C1q complement component and -antibodies reflect SLE activity and kidney involvement.
        Clin Rheumatol. 2006; 25: 532-536
        • Wu F.Q.
        • Zhao Q.
        • Cui X.D.
        • Zhang W.
        C1q and anti-C1q antibody levels are correlated with disease severity in Chinese pediatric systemic lupus erythematosus.
        Rheumatol Int. 2011; 31: 501-505
        • DeLong E.R.
        • DeLong D.M.
        • Clarke-Pearson D.L.
        Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.
        Biometrics. 1988; 44: 837-845
      1. Examination Committee of Criteria for 'Obesity Disease' in Japan; Japan Society for the Study of Obesity: new criteria for 'obesity disease' in Japan.
        Circ J. 2002; 66: 987-992
        • Gabrielsson B.G.
        • Johansson J.M.
        • Lönn M.
        • et al.
        High expression of complement components in omental adipose tissue in obese men.
        Obes Res. 2003; 11: 699-708
        • Zhang J.
        • Wright W.
        • Bernlohr D.A.
        • et al.
        Alterations of the classic pathway of complement in adipose tissue of obesity and insulin resistance.
        Am J Physiol Endocrinol Metab. 2007; 292: E1433-E1440
        • Esterbauer H.
        • Krempler F.
        • Oberkofler H.
        • Patsch W.
        The complement system: a pathway linking host defence and adipocyte biology.
        Eur J Clin Invest. 1999; 29: 653-656
        • Tamba S.
        • Nishizawa H.
        • Funahashi T.
        • et al.
        Relationship between the serum uric acid level, visceral fat accumulation and serum adiponectin concentration in Japanese men.
        Intern Med. 2008; 47: 1175-1180
        • Ouchi N.
        • Walsh K.
        Adiponectin as an anti-inflammatory factor.
        Clin Chim Acta. 2007; 380: 24-30
        • Peake P.W.
        • Shen Y.
        • Walther A.
        • Charlesworth J.A.
        Adiponectin binds C1q and activates the classical pathway of complement.
        Biochem Biophys Res Commun. 2008; 367: 560-565
        • Peake P.
        • Shen Y.
        Factor H binds to the N-terminus of adiponectin and modulates complement activation.
        Biochem Biophys Res Commun. 2010; 397: 361-366