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. 1983 Jun;111(3):288–297.

Enriched lipid diet accelerates lupus nephritis in NZB x W mice. Synergistic action of immune complexes and lipid in glomerular injury.

V E Kelley, S Izui
PMCID: PMC1916288  PMID: 6344647

Abstract

The effect of a lipid-rich diet was investigated in autoimmune NZB x W mice with immune complex lupus nephritis. Mice on an enriched lipid diet died sooner than controls. This increase in dietary fat elevated serum cholesterol levels and was associated with an accelerated loss of renal function. Ultrastructural examination of glomeruli revealed lipid in the peripheral loops and mesangium adjacent to immune deposits. Increased lipid accumulation was confirmed by histochemical staining and biochemical extraction. Accelerated disease was not related to changes in immune parameters. Thus, a high lipid consumption accelerated lupus nephritis by a local vascular effect and not by a systemic influence on the immune response. Therefore, in our system, a combined immunologic and lipid glomerular capillary insult caused a more rapidly progressive renal disease than immune complex injury alone.

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Selected References

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  1. BAXTER J. H. Hyperlipoproteinemia in nephrosis. Arch Intern Med. 1962 Jun;109:742–757. doi: 10.1001/archinte.1962.03620180104012. [DOI] [PubMed] [Google Scholar]
  2. Berlyne G. M., Mallick N. P. Ischaemic heart-disease as a complication of nephrotic syndrome. Lancet. 1969 Aug 23;2(7617):399–400. doi: 10.1016/s0140-6736(69)90110-x. [DOI] [PubMed] [Google Scholar]
  3. Curry R. C., Jr, Roberts W. C. Status of the coronary arteries in the nephrotic syndrome. Analysis of 20 necropsy patients aged 15 to 35 years to determine if coronary atherosclerosis is accelerated. Am J Med. 1977 Aug;63(2):183–192. doi: 10.1016/0002-9343(77)90231-5. [DOI] [PubMed] [Google Scholar]
  4. FOLCH J., LEES M., SLOANE STANLEY G. H. A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem. 1957 May;226(1):497–509. [PubMed] [Google Scholar]
  5. Fernandes G., Friend P., Yunis E. J., Good R. A. Influence of dietary restriction on immunologic function and renal disease in (NZB x NZW) F1 mice. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1500–1504. doi: 10.1073/pnas.75.3.1500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friend P. S., Fernandes G., Good R. A., Michael A. F., Yunis E. J. Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse. Lab Invest. 1978 Jun;38(6):629–632. [PubMed] [Google Scholar]
  7. Hurd E. R., Johnston J. M., Okita J. R., MacDonald P. C., Ziff M., Gilliam J. W. Prevention of glomerulonephritis and prolonged survival in New Zealand Black/New Zealand White F1 hybrid mice fed an essential fatty acid-deficient diet. J Clin Invest. 1981 Feb;67(2):476–485. doi: 10.1172/JCI110056. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Izui S., Fernandes G., Hara I., McConahey P. J., Jensen F. C., Dixon F. J., Good R. A. Low-calorie diet selectively reduces expression of retroviral envelope glycoprotein gp70 in sera of NZB x NZW F1 hybrid mice. J Exp Med. 1981 Oct 1;154(4):1116–1124. doi: 10.1084/jem.154.4.1116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Izui S., Kelley V. E., McConahey P. J., Dixon F. J. Selective suppression of retroviral gp70-anti-gp70 immune complex formation by prostaglandin E1 in murine systemic lupus erythematosus. J Exp Med. 1980 Dec 1;152(6):1645–1658. doi: 10.1084/jem.152.6.1645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Izui S., Lambert P. H., Miescher P. A. Determination of anti-DNA antibodies by a modified 125I-labelled DNA-binding test. Elimination of non-specific binding of DNA to non-immunoglobulin basic proteins by using an anionic detergent. Clin Exp Immunol. 1976 Dec;26(3):425–430. [PMC free article] [PubMed] [Google Scholar]
  11. Izui S., McConahey P. J., Theofilopoulos A. N., Dixon F. J. Association of circulating retroviral gp70-anti-gp70 immune complexes with murine systemic lupus erythematosus. J Exp Med. 1979 May 1;149(5):1099–1116. doi: 10.1084/jem.149.5.1099. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kelley V. E., Cavallo T. An ultrastructural study of the glomerular slit diaphragm in New Zealand black/white mice. Lab Invest. 1976 Sep;35(3):213–220. [PubMed] [Google Scholar]
  13. Kelley V. E., Winkelstein A., Izui S. Effect of prostaglandin E on immune complex nephritis in NZB/W mice. Lab Invest. 1979 Dec;41(6):531–537. [PubMed] [Google Scholar]
  14. Levy J. A., Ibrahim A. B., Shirai T., Ohta K., Nagasawa R., Yoshida H., Estes J., Gardner M. Dietary fat affects immune response, production of antiviral factors, and immune complex disease in NZB/NZW mice. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1974–1978. doi: 10.1073/pnas.79.6.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. McKenzie I. F., Nestel P. J. Studies on the turnover of triglyceride and esterified cholesterol in subjects with the nephrotic syndrome. J Clin Invest. 1968 Jul;47(7):1685–1695. doi: 10.1172/JCI105859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Minick C. R., Murphy G. E., Campbell W. G., Jr Experimental induction of athero-arteriosclerosis by the synergy of allergic injury to arteries and lipid-rich diet. I. Effect of repeated injections of horse serum in rabbits fed a dietary cholesterol supplement. J Exp Med. 1966 Oct 1;124(4):635–652. doi: 10.1084/jem.124.4.635. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Theofilopoulos A. N., Wilson C. B., Dixon F. J. The Raji cell radioimmune assay for detecting immune complexes in human sera. J Clin Invest. 1976 Jan;57(1):169–182. doi: 10.1172/JCI108257. [DOI] [PMC free article] [PubMed] [Google Scholar]

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