Top

Published in:

01-04-2011

Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models

Authors: Jennifer Parker, Hanni Menn-Josephy, Bari Laskow, Yukihiro Takemura, Tamar Aprahamian

Published in: Journal of Clinical Immunology | Issue 2/2011

Abstract

Adiponectin is an adipocyte-derived cytokine with anti-inflammatory properties. Paradoxically, circulating adiponectin levels are increased in a number of inflammatory diseases. Thus, we sought to define the role of adiponectin deficiency in mouse models of autoimmunity. Adiponectin-deficient mice on a C57BL/6 background do not develop an autoimmune phenotype. Autoimmunity was also not observed in adiponectin-deficient mice generated on the permissive MRL background. However, adiponectin deficiency exacerbated the autoimmune phenotype of MRL-lpr mice. Compared with MRL-lpr mice, MRL-lpr.apn^−/− mice displayed greater lymphadenopathy and splenomegaly, as well as increased anti-nuclear antibody and anti-dsDNA production. In addition, evaluation of the kidney revealed larger glomerular tuft size, crescent formation, increased IgG and C3 deposits, and mesangial expansion in the MRL-lpr.apn^−/− mice. The effects of adiponectin deficiency on the autoimmune phenotypes were more pronounced in female versus male mice. These data show that, while adiponectin deficiency is not sufficient to confer autoimmunity, adiponectin acts as a negative modulator of the autoimmune phenotype in a murine model of lupus.

Berg AH, Scherer PE. Adipose tissue, inflammation, and cardiovascular disease. Circ Res. 2005;96:939–49.PubMedCrossRef

Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol. 2003;14:561–6.PubMedCrossRef

Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun. 1999;257:79–83.PubMedCrossRef

Ryo M, Nakamura T, Kihara S, Kumada M, Shibazaki S, Takahashi M, et al. Adiponectin as a biomarker of the metabolic syndrome. Circ J. 2004;68:975–81.PubMedCrossRef

Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2003;301:1045–50.PubMedCrossRef

Kappes A, Loffler G. Influences of ionomycin, dibutyryl-cycloAMP and tumour necrosis factor-alpha on intracellular amount and secretion of apM1 in differentiating primary human preadipocytes. Horm Metab Res. 2000;32:548–54.PubMedCrossRef

Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, et al. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes. 2001;50:2094–9.PubMedCrossRef

Isobe T, Saitoh S, Takagi S, Takeuchi H, Chiba Y, Katoh N, et al. Influence of gender, age and renal function on plasma adiponectin level: the Tanno and Sobetsu study. Eur J Endocrinol. 2005;153:91–8.PubMedCrossRef

Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, et al. Adiponectin and protection against type 2 diabetes mellitus. Lancet. 2003;361:226–8.PubMedCrossRef

10.

Iwashima Y, Horio T, Kumada M, Suzuki Y, Kihara S, Rakugi H, et al. Adiponectin and renal function, and implication as a risk of cardiovascular disease. Am J Cardiol. 2006;98:1603–8.PubMedCrossRef

11.

Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291:1730–7.PubMedCrossRef

12.

Atzmon G, Pollin TI, Crandall J, Tanner K, Schechter CB, Scherer PE, et al. Adiponectin levels and genotype: a potential regulator of life span in humans. J Gerontol A Biol Sci Med Sci. 2008;63:447–53.PubMed

13.

Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8:731–7.PubMedCrossRef

14.

Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension. 2006;47:1108–16.PubMedCrossRef

15.

Okamoto Y, Folco E, Minami M, Wara A, Feinberg M, Sukhova G, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res. 2008;102:218–25.PubMedCrossRef

16.

Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106:2767–70.PubMedCrossRef

17.

Takemura Y, Ouchi N, Shibata R, Aprahamian T, Kirber MT, Summer RS, et al. Adiponectin modulates inflammatory reactions via calreticulin receptor-dependent clearance of early apoptotic bodies. J Clin Invest. 2007;117:375–86.PubMedCrossRef

18.

Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR, et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med. 2004;10:1384–9.PubMedCrossRef

19.

Shibata R, Ouchi N, Kihara S, Sato K, Funahashi T, Walsh K. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem. 2004;279:28670–4.PubMedCrossRef

20.

Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005;11:1096–103.PubMedCrossRef

21.

Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J, et al. Association between adiponectin and mediators of inflammation in obese women. Diabetes. 2003;52:942–7.PubMedCrossRef

22.

Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA. 2003;289:1799–804.PubMedCrossRef

23.

Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, et al. Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diab Care. 2003;26:1745–51.CrossRef

24.

Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation. 2003;107:671–4.PubMedCrossRef

25.

Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, 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;96:1723–32.PubMed

26.

Fantuzzi G. Adiponectin and inflammation: consensus and controversy. J Allergy Clin Immunol. 2008;121:326–30.PubMedCrossRef

27.

Sada KE, Yamasaki Y, Maruyama M, Sugiyama H, Yamamura M, Maeshima Y, et al. Altered levels of adipocytokines in association with insulin resistance in patients with systemic lupus erythematosus. J Rheumatol. 2006;33:1545–52.PubMed

28.

Schaffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Scholmerich J, et al. Adipocytokines in synovial fluid. JAMA. 2003;290:1709–10.PubMedCrossRef

29.

Furuta M, Tamai M, Hanabusa T, Yamamoto Y, Nanjo K, Sanke T. Serum adiponectin is associated with fasting serum C-peptide in non-obese diabetic patients. Diabetes Res Clin Pract. 2006;72:302–7.PubMedCrossRef

30.

Perseghin G, Lattuada G, Danna M, Sereni LP, Maffi P, De Cobelli F, et al. Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes. Am J Physiol Endocrinol Metab. 2003;285:E1174–81.PubMed

31.

Bickerstaff MC, Botto M, Hutchinson WL, Herbert J, Tennent GA, Bybee A, et al. Serum amyloid P component controls chromatin degradation and prevents antinuclear autoimmunity. Nat Med. 1999;5:694–7.PubMedCrossRef

32.

Cohen PL, Eisenberg RA. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol. 1991;9:243–69.PubMedCrossRef

33.

Watanabe-Fukunaga R, Brannan CI, Copeland NG, Jenkins NA, Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992;356:314–7.PubMedCrossRef

34.

Theofilopoulos AN, Dixon FJ. Murine models of systemic lupus erythematosus. Adv Immunol. 1985;37:269–390.PubMedCrossRef

35.

Aprahamian T, Bonegio RG, Richez C, Yasuda K, Chiang LK, Sato K, et al. The peroxisome proliferator-activated receptor gamma agonist rosiglitazone ameliorates murine lupus by induction of adiponectin. J Immunol. 2009;182:340–6.PubMed

36.

Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995;270:26746–9.PubMedCrossRef

37.

Suzuki S, Wilson-Kubalek EM, Wert D, Tsao TS, Lee DH. The oligomeric structure of high molecular weight adiponectin. FEBS Lett. 2007;581:809–14.PubMedCrossRef

38.

Peake PW, Shen Y, Walther A, Charlesworth JA. Adiponectin binds C1q and activates the classical pathway of complement. Biochem Biophys Res Commun. 2008;367:560–5.PubMedCrossRef

39.

Rovin BH, Song H, Hebert LA, Nadasdy T, Nadasdy G, Birmingham DJ, et al. Plasma, urine, and renal expression of adiponectin in human systemic lupus erythematosus. Kidney Int. 2005;68:1825–33.PubMedCrossRef

40.

Song H, Chan J, Rovin BH. Induction of chemokine expression by adiponectin in vitro is isoform dependent. Transl Res. 2009;154:18–26.PubMedCrossRef

41.

Vadacca M, Margiotta D, Rigon A, Cacciapaglia F, Coppolino G, Amoroso A, et al. Adipokines and systemic lupus erythematosus: relationship with metabolic syndrome and cardiovascular disease risk factors. J Rheumatol. 2009;36:295–7.PubMedCrossRef

42.

Bruce CR, Mertz VA, Heigenhauser GJ, Dyck DJ. The stimulatory effect of globular adiponectin on insulin-stimulated glucose uptake and fatty acid oxidation is impaired in skeletal muscle from obese subjects. Diabetes. 2005;54:3154–60.PubMedCrossRef

43.

Panchapakesan U, Chen XM, Pollock CA. Drug insight: thiazolidinediones and diabetic nephropathy—relevance to renoprotection. Nat Clin Pract Nephrol. 2005;1:33–43.PubMedCrossRef

44.

Mullen KL, Smith AC, Junkin KA, Dyck DJ. Globular adiponectin resistance develops independently of impaired insulin-stimulated glucose transport in soleus muscle from high-fat fed rats. Am J Physiol Endocrinol Metab. 2007;293:E83–90.PubMedCrossRef

45.

Zandman-Goddard G, Peeva E, Shoenfeld Y. Gender and autoimmunity. Autoimmun Rev. 2007;6:366–72.PubMedCrossRef

Title: Modulation of Lupus Phenotype by Adiponectin Deficiency in Autoimmune Mouse Models
Authors: Jennifer Parker
Hanni Menn-Josephy
Bari Laskow
Yukihiro Takemura
Tamar Aprahamian
Publication date: 01-04-2011
Publisher: Springer US
Published in: Journal of Clinical Immunology / Issue 2/2011
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-010-9486-2

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2011

Enhanced Th17 Phenotype in Uninfected Neonates Born from Viremic HIV-1-Infected Pregnant Women

FOXP3, IL-10, and TGF-β Genes Expression in Children with IgE-Dependent Food Allergy

ICF Syndrome in Saudi Arabia: Immunological, Cytogenetic and Molecular Analysis

Oxytetracycline Attenuates Allergic Airway Inflammation in Mice via Inhibition of the NF-κB Pathway

CD8+ T Cells in Facioscapulohumeral Muscular Dystrophy Patients with Inflammatory Features at Muscle MRI

Hepatitis B e-antigen Persistency is Associated with the Properties of HBV-Specific CD8 T Cells in CHB Patients

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials