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Gene Review

Cfd  -  complement factor D (adipsin)

Mus musculus

Synonyms: 28 kDa adipocyte protein, Adipsin, Adn, C3 convertase activator, Complement factor D, ...
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Disease relevance of Cfd

  • RESULTS: MRL/lpr Df-/- mice had similar glomerular IgG deposition, proteinuria and autoantibody levels, as Df+/+ and Df+/- littermates [1].
  • Adipsin is a serine protease that is secreted by adipocytes into the bloodstream; it is deficient in several animal models of obesity, representing a striking example of defective gene expression in this disorder [2].
  • The mutant mice have no apparent abnormality in development and their body weights are similar to those of factor D-sufficient littermates [3].
  • The serine protease inhibitor BCX 1470, which blocks the esterolytic and hemolytic activities of the complement enzymes Cls and factor D in vitro, also blocked development of RPA-induced edema in the rat [4].
  • Hypoxia up-regulates mouse vascular endothelial growth factor D promoter activity in rat pulmonary microvascular smooth-muscle cells [5].

High impact information on Cfd

  • Activated adipsin has little or no proteolytic activity toward most substrates but has the same activity as human complement factor D, cleaving complement factor B when it is complexed with activated complement component C3 [2].
  • Pluripotent stem cell lines were isolated with homologously recombined insertions at three different loci: c-fos, which is expressed at a low level in ES cells, and two genes, adipsin and adipocyte P2 (aP2), which are transcribed specifically in adipose cells and are not expressed at detectable levels in ES cells [6].
  • Adipsin and complement factor D activity: an immune-related defect in obesity [2].
  • Like authentic factor D, adipsin can activate the alternative pathway of complement, resulting in red blood cell lysis [2].
  • Adipsin, a serine protease homolog, is synthesized and secreted by adipose cells and is found in the bloodstream [7].

Chemical compound and disease context of Cfd


Biological context of Cfd


Anatomical context of Cfd


Associations of Cfd with chemical compounds

  • We used mice deficient in C1q, factor D, C3, and CD59, and compared them with strain-matched controls [18].
  • However, glomerular C3 deposition, serum creatinine levels, and pathologic renal disease were significantly reduced in Df-/- mice [1].
  • Genetic deficiencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread [19].
  • The effect is factor D- and, at least in part, C5-dependent, indicating that local alternative pathway activation is essential [20].
  • These results show that adipsin is a novel serine protease gene whose expression is regulated by a macrophage-derived factor which modulates expression of other adipocyte-specific RNAs [10].

Regulatory relationships of Cfd

  • Macrophage factor B was cleaved and activated to factor Bb- and Ba-like fragments by factor D and cobra venom factor [21].
  • However, TGF-alpha repressed the differentiation of the preadipocyte cell line 3T3-F442A in a dose-dependent and reversible manner as judged by morphological conversion and diminished expression of mRNAs encoding the adipocyte-specific markers adipsin and glycerophosphate dehydrogenase [22].
  • However, sterol regulatory element-binding protein-1, apolipoprotein A4, and adipsin mRNAs were significantly induced in ICAM-1-deficient livers, suggesting that these genes and their associated pathways may be involved in the acute diet response observed in the knockout mice [23].

Other interactions of Cfd

  • On differentiation, mRNA for C3 (fivefold) and factor D (> 50-fold) increased, whereas stimulation with tumour necrosis factor (TNF)-alpha and interleukin (IL) 1 beta led to eightfold increases in factor B mRNA [13].
  • METHODS: Df-deficient mice were backcrossed with MRL/lpr mice for four to nine generations [1].
  • Low level constitutive expression of PPAR gamma in 3T3-L1 adipocytes (at levels approximately 2- to 3-fold higher than in preadipocytes) partially blocked the inhibitory effect of TNF alpha on aP2 and adipsin expression [24].
  • We find that ACRP30 overlaps with adipsin in intracellular compartments distinct from Glut4, but nonetheless exhibits insulin-stimulated secretion from cells [25].
  • Expression of two adipocyte-specific factors, adipsin and leptin, is significantly reduced in the WAT of C/ebpalpha(beta/beta) mice [26].

Analytical, diagnostic and therapeutic context of Cfd


  1. Effects of complement factor D deficiency on the renal disease of MRL/lpr mice. Elliott, M.K., Jarmi, T., Ruiz, P., Xu, Y., Holers, V.M., Gilkeson, G.S. Kidney Int. (2004) [Pubmed]
  2. Adipsin and complement factor D activity: an immune-related defect in obesity. Rosen, B.S., Cook, K.S., Yaglom, J., Groves, D.L., Volanakis, J.E., Damm, D., White, T., Spiegelman, B.M. Science (1989) [Pubmed]
  3. Complement activation in factor D-deficient mice. Xu, Y., Ma, M., Ippolito, G.C., Schroeder, H.W., Carroll, M.C., Volanakis, J.E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  4. The Arthus reaction in rodents: species-specific requirement of complement. Szalai, A.J., Digerness, S.B., Agrawal, A., Kearney, J.F., Bucy, R.P., Niwas, S., Kilpatrick, J.M., Babu, Y.S., Volanakis, J.E. J. Immunol. (2000) [Pubmed]
  5. Hypoxia up-regulates mouse vascular endothelial growth factor D promoter activity in rat pulmonary microvascular smooth-muscle cells. Teng, X., Li, D., Johns, R.A. Chest (2002) [Pubmed]
  6. Targeting of nonexpressed genes in embryonic stem cells via homologous recombination. Johnson, R.S., Sheng, M., Greenberg, M.E., Kolodner, R.D., Papaioannou, V.E., Spiegelman, B.M. Science (1989) [Pubmed]
  7. Severely impaired adipsin expression in genetic and acquired obesity. Flier, J.S., Cook, K.S., Usher, P., Spiegelman, B.M. Science (1987) [Pubmed]
  8. Independent regulation of adipose tissue-specificity and obesity response of the adipsin promoter in transgenic mice. Platt, K.A., Claffey, K.P., Wilkison, W.O., Spiegelman, B.M., Ross, S.R. J. Biol. Chem. (1994) [Pubmed]
  9. Reduced adipsin expression in murine obesity: effect of age and treatment with the sympathomimetic-thermogenic drug mixture ephedrine and caffeine. Lowell, B.B., Napolitano, A., Usher, P., Dulloo, A.G., Rosen, B.S., Spiegelman, B.M., Flier, J.S. Endocrinology (1990) [Pubmed]
  10. Adipsin, the adipocyte serine protease: gene structure and control of expression by tumor necrosis factor. Min, H.Y., Spiegelman, B.M. Nucleic Acids Res. (1986) [Pubmed]
  11. Regulation of preadipocyte factor-1 gene expression during 3T3-L1 cell differentiation. Boney, C.M., Fiedorek, F.T., Paul, S.R., Gruppuso, P.A. Endocrinology (1996) [Pubmed]
  12. Surface loops adjacent to the cation-binding site of the complement factor B von Willebrand factor type A module determine C3b binding specificity. Tuckwell, D.S., Xu, Y., Newham, P., Humphries, M.J., Volanakis, J.E. Biochemistry (1997) [Pubmed]
  13. Detection and quantification of the control proteins of the alternative pathway of complement in 3T3-L1 adipocytes. Peake, P.W., O'Grady, S., Pussell, B.A., Charlesworth, J.A. Eur. J. Clin. Invest. (1997) [Pubmed]
  14. Growth-supporting activity of fragment Ba of the human alternative complement pathway for activated murine B lymphocytes. Praz, F., Ruuth, E. J. Exp. Med. (1986) [Pubmed]
  15. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. White, R.T., Damm, D., Hancock, N., Rosen, B.S., Lowell, B.B., Usher, P., Flier, J.S., Spiegelman, B.M. J. Biol. Chem. (1992) [Pubmed]
  16. Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Cook, K.S., Min, H.Y., Johnson, D., Chaplinsky, R.J., Flier, J.S., Hunt, C.R., Spiegelman, B.M. Science (1987) [Pubmed]
  17. Vascular endothelial growth factor D is dispensable for development of the lymphatic system. Baldwin, M.E., Halford, M.M., Roufail, S., Williams, R.A., Hibbs, M.L., Grail, D., Kubo, H., Stacker, S.A., Achen, M.G. Mol. Cell. Biol. (2005) [Pubmed]
  18. Complement activation contributes to both glomerular and tubulointerstitial damage in adriamycin nephropathy in mice. Turnberg, D., Lewis, M., Moss, J., Xu, Y., Botto, M., Cook, H.T. J. Immunol. (2006) [Pubmed]
  19. Protective immune responses against West Nile virus are primed by distinct complement activation pathways. Mehlhop, E., Diamond, M.S. J. Exp. Med. (2006) [Pubmed]
  20. Decay-accelerating factor modulates induction of T cell immunity. Heeger, P.S., Lalli, P.N., Lin, F., Valujskikh, A., Liu, J., Muqim, N., Xu, Y., Medof, M.E. J. Exp. Med. (2005) [Pubmed]
  21. Factor B, the complement alternative pathway serine proteinase, is a major constitutive protein synthesized and secreted by resident and elicited mouse macrophages. Sundsmo, J.S., Chin, J.R., Papin, R.A., Fair, D.S., Werb, Z. J. Exp. Med. (1985) [Pubmed]
  22. Regulation of fat and muscle development by transforming growth factor alpha in transgenic mice and in cultured cells. Luetteke, N.C., Lee, D.C., Palmiter, R.D., Brinster, R.L., Sandgren, E.P. Cell Growth Differ. (1993) [Pubmed]
  23. Diet-induced obesity and hepatic gene expression alterations in C57BL/6J and ICAM-1-deficient mice. Gregoire, F.M., Zhang, Q., Smith, S.J., Tong, C., Ross, D., Lopez, H., West, D.B. Am. J. Physiol. Endocrinol. Metab. (2002) [Pubmed]
  24. Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Zhang, B., Berger, J., Hu, E., Szalkowski, D., White-Carrington, S., Spiegelman, B.M., Moller, D.E. Mol. Endocrinol. (1996) [Pubmed]
  25. ACRP30 is secreted from 3T3-L1 adipocytes via a Rab11-dependent pathway. Clarke, M., Ewart, M.A., Santy, L.C., Prekeris, R., Gould, G.W. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  26. C/EBPbeta, when expressed from the C/ebpalpha gene locus, can functionally replace C/EBPalpha in liver but not in adipose tissue. Chen, S.S., Chen, J.F., Johnson, P.F., Muppala, V., Lee, Y.H. Mol. Cell. Biol. (2000) [Pubmed]
  27. Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D. Pascual, M., Catana, E., White, T., Spiegelman, B.M., Schifferli, J.A. Eur. J. Immunol. (1993) [Pubmed]
  28. Adrenal glucocorticoids regulate adipsin gene expression in genetically obese mice. Spiegelman, B.M., Lowell, B., Napolitano, A., Dubuc, P., Barton, D., Francke, U., Groves, D.L., Cook, K.S., Flier, J.S. J. Biol. Chem. (1989) [Pubmed]
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