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Exp Clin Endocrinol Diabetes 2013; 121(04): 194-200
DOI: 10.1055/s-0032-1333231
Article
© J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

Inflammatory Markers and Adipokines Alter Adipocyte-derived ASP Production Through Direct and Indirect Immune Interaction

H. Lu   *
1   Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada
2   Department of Pediatrics, Tongji Hospital, HuaZhong University of Science and Technology, Wuhan, Hubei, P. R. China
,
D. Gauvreau   *
1   Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada
,
F.-Q. Tom
1   Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada
,
M. Lapointe
1   Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada
,
X. P. Luo
2   Department of Pediatrics, Tongji Hospital, HuaZhong University of Science and Technology, Wuhan, Hubei, P. R. China
,
K. Cianflone
1   Centre de Recherche Institut Universitaire de Cardiologie & Pneumologie de Québec, Université Laval, Québec, Canada
› Author Affiliations
Further Information

Publication History

received 09 August 2012
first decision 01 November 2012

accepted 17 December 2012

Publication Date:
21 February 2013 (online)

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Abstract

Obesity and related metabolic diseases are associated with chronic low-grade inflammation, characterized by increased pro-inflammatory proteins. Several studies have demonstrated increases in acylation stimulating protein (ASP) and its precursor protein C3 in obesity, diabetes and dyslipidemia. To evaluate the effects of acute inflammatory factors and adipokines on ASP production and potential mechanisms of action, 3T3-L1 adipocytes were treated for 24 h with adipokines, cytokines, macrophage-conditioned media and direct co-culture with J774 macrophages. ASP and C3 in the media were evaluated in relation to changes in adipocyte lipid metabolism (cellular triglyceride stores). Leptin, adiponectin, IL-10, LPS and TNF-α increased ASP production (151%, 153%, 190%, 318%, 134%, P<0.05, respectively,). C5a and RANTES (Regulated and normal T cell expressed and secreted) decreased ASP production ( − 34%,  − 47%, P<0.05), which was also associated with a decrease in the precursor protein C3 ( − 39% to  − 51%, P<0.01), while keratinocyte chemoattractant (KC; murine IL-8 ortholog) had no effect on ASP and C3 secretion. By contrast, apelin, omentin and visfatin also decreased ASP ( − 27%,  − 49%,  − 22%, P<0.05), but without changes in precursor protein C3 secretion. Macrophage-conditioned media alone had little effect on C3 or ASP, while co-culture of adipocytes with macrophages markedly increased ASP and C3 production (272%, 167%, P<0.05). These in vitro results suggest various metabolic hormones and inflammatory factors can affect ASP production through increased precursor C3 production and/or by changing the rate of C3 conversion to ASP. As an adipokine, ASP could constitute a new link between adipocytes and macrophages.

Key words

adipocytokines - inflammation - obesity
*

* Shared first author.


 

  • References

  • 1 Weisberg SP, McCann D, Desai M et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112: 1796-1808
    CrossrefPubMedGoogle Scholar
  • 2 Hotamisligil GS, Arner P, Caro JF et al. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 1995; 95: 2409-2415
    CrossrefPubMedGoogle Scholar
  • 3 Sartipy P, Loskutoff DJ. Expression profiling identifies genes that continue to respond to insulin in adipocytes made insulin-resistant by treatment with tumor necrosis factor-alpha. J Biol Chem 2003; 278: 52298-52306
    CrossrefPubMedGoogle Scholar
  • 4 Kim CS, Park HS, Kawada T et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond) 2006; 30: 1347-1355
    CrossrefPubMedGoogle Scholar
  • 5 Zeyda M, Stulnig TM. Adipose tissue macrophages. Immunol Lett 2007; 112: 61-67
    CrossrefPubMedGoogle Scholar
  • 6 Gao Y, Gauvreau D, Cianflone K. Hormone and pharmaceutical regulation of ASP production in 3T3-L1 adipocytes. J Cell Biochem 2010; 109: 896-905
    PubMedGoogle Scholar
  • 7 Murray I, Sniderman AD, Cianflone K. Enhanced triglyceride clearance with intraperitoneal human acylation stimulating protein in C57BL/6 mice. Am J Physiol 1999; 277: E474-E480
    PubMedGoogle Scholar
  • 8 Cianflone K, Xia Z, Chen LY. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta 2003; 1609: 127-143
    CrossrefPubMedGoogle Scholar
  • 9 Schrauwen P, Hesselink MK, Jain M et al. Acylation-stimulating protein: effect of acute exercise and endurance training. Int J Obes (Lond) 2005; 29: 632-638
    CrossrefPubMedGoogle Scholar
  • 10 Cianflone K, Maslowska M. Differentiation-induced production of ASP in human adipocytes. Eur J Clin Invest 1995; 25: 817-825
    CrossrefPubMedGoogle Scholar
  • 11 Kalant D, MacLaren R, Cui W et al. C5L2 is a functional receptor for acylation-stimulating protein. J Biol Chem 2005; 280: 23936-23944
    CrossrefPubMedGoogle Scholar
  • 12 Zhu S, Sun F, Li W et al. Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes. Mol Cell Biochem 2011; 353: 305-313
    CrossrefPubMedGoogle Scholar
  • 13 Sommer G, Garten A, Petzold S et al. Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. Clin Sci (Lond) 2008; 115: 13-23
    CrossrefPubMedGoogle Scholar
  • 14 Yang RZ, Lee MJ, Hu H et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006; 290: E1253-E1261
    CrossrefPubMedGoogle Scholar
  • 15 Whitehead JP, Richards AA, Hickman IJ et al. Adiponectin – a key adipokine in the metabolic syndrome. Diabetes Obes Metab 2006; 8: 264-280
    CrossrefPubMedGoogle Scholar
  • 16 Brochu-Gaudreau K, Rehfeldt C, Blouin R et al. Adiponectin action from head to toe. Endocrine 2010; 37: 11-32
    CrossrefPubMedGoogle Scholar
  • 17 Peake PW, Shen Y, Walther A et al. Adiponectin binds C1q and activates the classical pathway of complement. Biochem Biophys Res Commun 2008; 367: 560-565
    CrossrefPubMedGoogle Scholar
  • 18 Bluher M, Fasshauer M, Tonjes A et al. Association of interleukin-6, C-reactive protein, interleukin-10 and adiponectin plasma concentrations with measures of obesity, insulin sensitivity and glucose metabolism. Exp Clin Endocrinol Diabetes 2005; 113: 534-537
    Article in Thieme ConnectPubMedGoogle Scholar
  • 19 Calcaterra V, De Amici M, Klersy C et al. Adiponectin, IL-10 and metabolic syndrome in obese children and adolescents. Acta Biomed 2009; 80: 117-123
    PubMedGoogle Scholar
  • 20 Dalmas E, Rouault C, Abdennour M et al. Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction. Am J Clin Nutr 2011; 94: 450-458
    CrossrefPubMedGoogle Scholar
  • 21 Belgardt BF, Bruning JC. CNS leptin and insulin action in the control of energy homeostasis. Ann N Y Acad Sci 2010; 1212: 97-113
    CrossrefPubMedGoogle Scholar
  • 22 Agrawal S, Gollapudi S, Su H et al. Leptin activates human B cells to secrete TNF-a, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway. J Clin Immunol 2011; 31: 472-478
    CrossrefPubMedGoogle Scholar
  • 23 Tulipano G, Vergoni AV, Soldi D et al. Characterization of the resistance to the anorectic and endocrine effects of leptin in obesity-prone and obesity-resistant rats fed a high-fat diet. J Endocrinol 2004; 183: 289-298
    CrossrefPubMedGoogle Scholar
  • 24 Waage A. Tumour necrosis factor and septic shock. Lancet 1998; 351: 603
    PubMedGoogle Scholar
  • 25 Sewter CP, Digby JE, Blows F et al. Regulation of tumour necrosis factor-alpha release from human adipose tissue in vitro. J Endocrinol 1999; 163: 33-38
    CrossrefPubMedGoogle Scholar
  • 26 Medina EA, Stanhope KL, Mizuno TM et al. Effects of tumor necrosis factor alpha on leptin secretion and gene expression: relationship to changes of glucose metabolism in isolated rat adipocytes. Int J Obes Relat Metab Disord 1999; 23: 896-903
    CrossrefPubMedGoogle Scholar
  • 27 Rosenstock M, Greenberg AS, Rudich A. Distinct long-term regulation of glycerol and non-esterified fatty acid release by insulin and TNF-alpha in 3T3-L1 adipocytes. Diabetologia 2001; 44: 55-62
    CrossrefPubMedGoogle Scholar
  • 28 Hirokawa J, Sakaue S, Furuya Y et al. Tumor necrosis factor-alpha regulates the gene expression of macrophage migration inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes. J Biochem 1998; 123: 733-739
    CrossrefPubMedGoogle Scholar
  • 29 Winkler G, Lakatos P, Salamon F et al. Elevated serum TNF-alpha level as a link between endothelial dysfunction and insulin resistance in normotensive obese patients. Diabet Med 1999; 16: 207-211
    CrossrefPubMedGoogle Scholar
  • 30 Creely SJ, McTernan PG, Kusminski CM et al. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes. Am J Physiol Endocrinol Metab 2007; 292: E740-E747
    CrossrefPubMedGoogle Scholar
  • 31 Vitseva OI, Tanriverdi K, Tchkonia TT et al. Inducible Toll-like receptor and NF-kappaB regulatory pathway expression in human adipose tissue. Obesity (Silver Spring) 2008; 16: 932-937
    CrossrefPubMedGoogle Scholar
  • 32 Kopp A, Buechler C, Neumeier M et al. Innate immunity and adipocyte function: ligand-specific activation of multiple Toll-like receptors modulates cytokine, adipokine, and chemokine secretion in adipocytes. Obesity (Silver Spring) 2009; 17: 648-656
    CrossrefPubMedGoogle Scholar
  • 33 Yang Y, Lu HL, Zhang J et al. Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes. Int J Obes (Lond) 2006; 30: 439-446
    CrossrefPubMedGoogle Scholar
  • 34 Gerhardt CC, Romero IA, Cancello R et al. Chemokines control fat accumulation and leptin secretion by cultured human adipocytes. Mol Cell Endocrinol 2001; 175: 81-92
    CrossrefPubMedGoogle Scholar
  • 35 Lu MM, Wang J, Pan HF et al. Increased serum RANTES in patients with systemic lupus erythematosus. Rheumatol Int 2012; 32: 1231-1233
    CrossrefPubMedGoogle Scholar
  • 36 Sewell DL, Nacewicz B, Liu F et al. Complement C3 and C5 play critical roles in traumatic brain cryoinjury: blocking effects on neutrophil extravasation by C5a receptor antagonist. J Neuroimmunol 2004; 155: 55-63
    CrossrefPubMedGoogle Scholar
  • 37 Ward PA. Functions of C5a receptors. J Mol Med (Berl) 2009; 87: 375-378
    CrossrefPubMedGoogle Scholar
  • 38 Suganami T, Ogawa Y. Adipose tissue macrophages: their role in adipose tissue remodeling. J Leukoc Biol 2010; 88: 33-39
    CrossrefPubMedGoogle Scholar
  • 39 Xu H, Barnes GT, Yang Q et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112: 1821-1830
    CrossrefPubMedGoogle Scholar
  • 40 Harford KA, Reynolds CM, McGillicuddy FC et al. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 2011; 70: 408-417
    CrossrefPubMedGoogle Scholar
  • 41 Maslowska M, Vu H, Phelis S et al. Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations. Eur J Clin Invest 1999; 29: 679-686
    CrossrefPubMedGoogle Scholar
  • 42 Cianflone K, Zhang XJ, Genest Jr J et al. Plasma acylation-stimulating protein in coronary artery disease. Arterioscler Thromb Vasc Biol 1997; 17: 1239-1244
    PubMedGoogle Scholar
  • 43 Wu Y, Zhang J, Wen Y et al. Increased acylation-stimulating protein, C-reactive protein, and lipid levels in young women with polycystic ovary syndrome. Fertil Steril 2009; 91: 213-219
    CrossrefPubMedGoogle Scholar
  • 44 MacLaren RE, Cui W, Lu H et al. Association of adipocyte genes with ASP expression: a microarray analysis of subcutaneous and omental adipose tissue in morbidly obese subjects. BMC Med Genomics 2010; 3: 3
    CrossrefPubMedGoogle Scholar