Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1993 Sep;92(3):1543–1547. doi: 10.1172/JCI116733

The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis.

A Baldo 1, A D Sniderman 1, S St-Luce 1, R K Avramoglu 1, M Maslowska 1, B Hoang 1, J C Monge 1, A Bell 1, S Mulay 1, K Cianflone 1
PMCID: PMC288301  PMID: 8376604

Abstract

We have previously characterized an activity from human plasma that markedly stimulates triglyceride synthesis in cultured human skin fibroblasts and human adipocytes. Based on its in vitro activity we named the active component acylation stimulating protein (ASP). The molecular identity of the active serum component has now been determined. NH2-terminal sequence analysis, ion spray ionization mass spectroscopy, and amino acid composition analysis all indicate that the active purified protein is a fragment of the third component of plasma complement, C3a-desArg. As well, reconstitution experiments with complement factors B, D, and complement C3, the components necessary to generate C3a, have confirmed the identity of ASP as C3a. ASP appears to be the final effector molecule generated by a novel regulatory system that modulates the rate of triglyceride synthesis in adipocytes.

Full text

PDF
1543

Images in this article

1545Image
on p.1545

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Caporale L. H., Tippett P. S., Erickson B. W., Hugli T. E. The active site of C3a anaphylatoxin. J Biol Chem. 1980 Nov 25;255(22):10758–10763. [PubMed] [Google Scholar]
  3. Choy L. N., Rosen B. S., Spiegelman B. M. Adipsin and an endogenous pathway of complement from adipose cells. J Biol Chem. 1992 Jun 25;267(18):12736–12741. [PubMed] [Google Scholar]
  4. Cianflone K. M., Maslowska M. H., Sniderman A. D. Impaired response of fibroblasts from patients with hyperapobetalipoproteinemia to acylation-stimulating protein. J Clin Invest. 1990 Mar;85(3):722–730. doi: 10.1172/JCI114497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cianflone K. M., Sniderman A. D., Walsh M. J., Vu H. T., Gagnon J., Rodriguez M. A. Purification and characterization of acylation stimulating protein. J Biol Chem. 1989 Jan 5;264(1):426–430. [PubMed] [Google Scholar]
  6. Cianflone K., Rodriguez M. A., Walsh M., Vu H., Sniderman A. D. The effect of a plasma protein fraction on lipid synthesis in cultured skin fibroblasts from normals and patients with hyperapobetalipoproteinemia. Clin Invest Med. 1988 Apr;11(2):99–107. [PubMed] [Google Scholar]
  7. Cianflone K., Vu H., Walsh M., Baldo A., Sniderman A. Metabolic response of Acylation Stimulating Protein to an oral fat load. J Lipid Res. 1989 Nov;30(11):1727–1733. [PubMed] [Google Scholar]
  8. Cook K. S., Groves D. L., Min H. Y., Spiegelman B. M. A developmentally regulated mRNA from 3T3 adipocytes encodes a novel serine protease homologue. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6480–6484. doi: 10.1073/pnas.82.19.6480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cook K. S., Min H. Y., Johnson D., Chaplinsky R. J., Flier J. S., Hunt C. R., Spiegelman B. M. Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science. 1987 Jul 24;237(4813):402–405. doi: 10.1126/science.3299705. [DOI] [PubMed] [Google Scholar]
  10. Flier J. S., Cook K. S., Usher P., Spiegelman B. M. Severely impaired adipsin expression in genetic and acquired obesity. Science. 1987 Jul 24;237(4813):405–408. doi: 10.1126/science.3299706. [DOI] [PubMed] [Google Scholar]
  11. Germinario R., Sniderman A. D., Manuel S., Lefebvre S. P., Baldo A., Cianflone K. Coordinate regulation of triacylglycerol synthesis and glucose transport by acylation-stimulating protein. Metabolism. 1993 May;42(5):574–580. doi: 10.1016/0026-0495(93)90215-a. [DOI] [PubMed] [Google Scholar]
  12. Hugli T. E. Human anaphylatoxin (C3a) from the third component of complement. Primary structure. J Biol Chem. 1975 Nov 10;250(21):8293–8301. [PubMed] [Google Scholar]
  13. Janatova J., Lorenz P. E., Schechter A. N., Prahl J. W., Tack B. F. Third component of human complement: appearance of a sulfhydryl group following chemical or enzymatic inactivation. Biochemistry. 1980 Sep 16;19(19):4471–4478. [PubMed] [Google Scholar]
  14. Kwiterovich P., Jr, Motevalli M., Miller M. Acylation-stimulatory activity in hyperapobetalipoproteinemic fibroblasts: enhanced cholesterol esterification with another serum basic protein, BP II. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8980–8984. doi: 10.1073/pnas.87.22.8980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  16. Mayorek N., Grinstein I., Bar-Tana J. Triacylglycerol synthesis in cultured rat hepatocytes. The rate-limiting role of diacylglycerol acyltransferase. Eur J Biochem. 1989 Jun 15;182(2):395–400. doi: 10.1111/j.1432-1033.1989.tb14844.x. [DOI] [PubMed] [Google Scholar]
  17. Pangburn M. K. Alternative pathway of complement. Methods Enzymol. 1988;162:639–653. doi: 10.1016/0076-6879(88)62106-9. [DOI] [PubMed] [Google Scholar]
  18. Schreiber R. D., Müller-Eberhard H. J. Assembly of the cytolytic alternative pathway of complement from 11 isolated plasma proteins. J Exp Med. 1978 Dec 1;148(6):1722–1727. doi: 10.1084/jem.148.6.1722. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sniderman A., Shapiro S., Marpole D., Skinner B., Teng B., Kwiterovich P. O., Jr Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (beta) lipoproteins]. Proc Natl Acad Sci U S A. 1980 Jan;77(1):604–608. doi: 10.1073/pnas.77.1.604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Teng B., Forse A., Rodriguez A., Sniderman A. Adipose tissue glyceride synthesis in patients with hyperapobetalipoproteinemia. Can J Physiol Pharmacol. 1988 Mar;66(3):239–242. doi: 10.1139/y88-040. [DOI] [PubMed] [Google Scholar]
  21. Teng B., Sniderman A. D., Soutar A. K., Thompson G. R. Metabolic basis of hyperapobetalipoproteinemia. Turnover of apolipoprotein B in low density lipoprotein and its precursors and subfractions compared with normal and familial hypercholesterolemia. J Clin Invest. 1986 Mar;77(3):663–672. doi: 10.1172/JCI112360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Toney K., Bateman A., Gagnon C., Bennett H. P. Aspartimide formation in the joining peptide sequence of porcine and mouse pro-opiomelanocortin. J Biol Chem. 1993 Jan 15;268(2):1024–1031. [PubMed] [Google Scholar]
  23. Van Harken D. R., Dixon C. W., Heimberg M. Hepatic lipid metabolism in experimental diabetes. V. The effect of concentration of oleate on metabolism of triglycerides and on ketogenesis. J Biol Chem. 1969 May 10;244(9):2278–2285. [PubMed] [Google Scholar]
  24. White R. T., Damm D., Hancock N., Rosen B. S., Lowell B. B., Usher P., Flier J. S., Spiegelman B. M. Human adipsin is identical to complement factor D and is expressed at high levels in adipose tissue. J Biol Chem. 1992 May 5;267(13):9210–9213. [PubMed] [Google Scholar]
  25. Yasruel Z., Cianflone K., Sniderman A. D., Rosenbloom M., Walsh M., Rodriguez M. A. Effect of acylation stimulating protein on the triacylglycerol synthetic pathway of human adipose tissue. Lipids. 1991 Jul;26(7):495–499. doi: 10.1007/BF02536592. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES