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Inflammation Research
Published in: Inflammation Research 10-11/2022

12-07-2022 | Lipolysis | Original Research Article

IL-25 directly modulates adipocyte function and inflammation through the regulation of adiponectin

Authors: Siranart Jeerawattanawart, Pilaiwan Siripurkpong, Sittiruk Roytrakul, Pornpimon Angkasekwinai

Published in: Inflammation Research | Issue 10-11/2022

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Abstract

Objective

This study aimed to investigate the direct role of IL-25 in modulating adipocyte function during homeostasis and low-grade inflammation induced by lipopolysaccharide (LPS).

Methods

The 3T3-L1 preadipocyte cell lines and primary cultures of adipose-derived stromal vascular precursor cells of wild-type and IL-17RB-deficient mice were used to determine the direct function of IL-25. The expression of IL-17RB in differentiating adipocyte was determined using real-time PCR and flow cytometry analysis. The effect of IL-25 on lipid accumulation, triglyceride content, lipolysis, glucose uptake, and adipokine expression in the mature adipocytes was evaluated. IL-25 modulating the expression of inflammatory cytokines in adipocytes induced by low dose LPS was determined using real-time PCR and ELISA.

Results

The receptor for IL-25 was up-regulated during adipocyte differentiation and IL-25 directly modulated adipocyte function by reducing lipid accumulation and triglyceride concentration and enhancing lipolysis without affecting an insulin-stimulated glucose uptake. Interestingly, IL-25 induced adiponectin secretion through the PI3K/AKT signaling pathway. In 3T3-L1 adipocytes under low-grade inflammation, IL-25 attenuated the expression of IL-6 and CCL5 through the induction of adiponectin.

Conclusion

Our studies suggest that IL-25 directly regulates adipocyte function by maintaining the adiponectin level during homeostasis and by alleviating inflammatory response through the regulation of adiponectin during low-grade inflammation in adipocytes.
Appendix
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Literature
1.
2.
3.
Stolarczyk E. Adipose tissue inflammation in obesity: a metabolic or immune response? Curr Opin Pharmacol. 2017;37:35–40.PubMedCrossRef
4.
Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993;259:87–91.PubMedCrossRef
5.
Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest. 1995;95:2111–9.PubMedPubMedCentralCrossRef
6.
Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998;83:847–50.PubMed
7.
Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–808.PubMedPubMedCentralCrossRef
8.
Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest. 2003;112:1821–30.PubMedPubMedCentralCrossRef
9.
Harkins JM, Moustaid-Moussa N, Chung YJ, Penner KM, Pestka JJ, North CM, et al. Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice. J Nutr. 2004;134:2673–7.PubMedCrossRef
10.
Kang YE, Kim JM, Joung KH, Lee JH, You BR, Choi MJ, et al. The roles of adipokines, proinflammatory cytokines, and adipose tissue macrophages in obesity-associated insulin resistance in modest obesity and early metabolic dysfunction. PLoS ONE. 2016;11: e0154003.PubMedPubMedCentralCrossRef
11.
12.
Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, et al. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature. 2015;519:242–6.PubMedCrossRef
13.
Wu D, Qiu Y. Type 2 immune regulation of adipose tissue homeostasis. Curr Opin Physio. 2019;12:20–5.CrossRef
14.
Michailidou Z, Gomez-Salazar M, Alexaki VI. Innate immune cells in the adipose tissue in health and metabolic disease. J Innate Immun. 2022;14:4–30.PubMedCrossRef
15.
Owyang AM, Zaph C, Wilson EH, Guild KJ, McClanahan T, Miller HR, et al. Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract. J Exp Med. 2006;203:843–9.PubMedPubMedCentralCrossRef
16.
Fallon PG, Ballantyne SJ, Mangan NE, Barlow JL, Dasvarma A, Hewett DR, et al. Identification of an interleukin (IL)-25-dependent cell population that provides IL-4, IL-5, and IL-13 at the onset of helminth expulsion. J Exp Med. 2006;203:1105–16.PubMedPubMedCentralCrossRef
17.
Angkasekwinai P, Park H, Wang YH, Wang YH, Chang SH, Corry DB, et al. Interleukin 25 promotes the initiation of proallergic type 2 responses. J Exp Med. 2007;204:1509–17.PubMedPubMedCentralCrossRef
18.
Ballantyne SJ, Barlow JL, Jolin HE, Nath P, Williams AS, Chung KF, et al. Blocking IL-25 prevents airway hyperresponsiveness in allergic asthma. J Allergy Clin Immunol. 2007;120:1324–31.PubMedCrossRef
19.
Zaph C, Du Y, Saenz SA, Nair MG, Perrigoue JG, Taylor BC, et al. Commensal-dependent expression of IL-25 regulates the IL-23-IL-17 axis in the intestine. J Exp Med. 2008;205:2191–8.PubMedPubMedCentralCrossRef
20.
Angkasekwinai P, Srimanote P, Wang YH, Pootong A, Sakolvaree Y, Pattanapanyasat K, et al. Interleukin-25 (IL-25) promotes efficient protective immunity against Trichinella spiralis infection by enhancing the antigen-specific IL-9 response. Infect Immun. 2013;81:3731–41.PubMedPubMedCentralCrossRef
21.
Martínez-Martínez E, Cachofeiro V, Rousseau E, Álvarez V, Calvier L, Fernández-Celis A, et al. Interleukin-33/ST2 system attenuates aldosterone-induced adipogenesis and inflammation. Mol Cell Endocrinol. 2015;411:20–7.PubMedCrossRef
22.
Miller AM, Asquith DL, Hueber AJ, Anderson LA, Holmes WM, McKenzie AN, et al. Interleukin-33 induces protective effects in adipose tissue inflammation during obesity in mice. Circ Res. 2010;107:650–8.PubMedPubMedCentralCrossRef
23.
Saxton SN, Whitley AS, Potter RJ. Interleukin-33 rescues perivascular adipose tissue anticontractile function in obesity. Am J Physiol-Heart Circ Physiol. 2020;319:H1387-h1397.PubMedCrossRef
24.
Hams E, Locksley RM, McKenzie AN, Fallon PG. Cutting edge: IL-25 elicits innate lymphoid type 2 and type II NKT cells that regulate obesity in mice. J Immunol. 2013;191:5349–53.PubMedCrossRef
25.
Feng J, Li L, Ou Z, Li Q, Gong B, Zhao Z, et al. IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity. Cell Mol Immunol. 2018;15:493–505.PubMedCrossRef
26.
Li L, Ma L, Zhao Z, Luo S, Gong B, Li J, et al. IL-25-induced shifts in macrophage polarization promote development of beige fat and improve metabolic homeostasis in mice. PLoS Biol. 2021;19: e3001348.PubMedPubMedCentralCrossRef
27.
Wang AJ, Yang Z. IL-25 or IL-17E protects against high-fat diet-induced hepatic steatosis in mice dependent upon IL-13 activation of STAT6. J Immunol (Baltimore, Md : 1950). 2015;195:4771–80.CrossRef
28.
Aune UL, Ruiz L, Kajimura S. Isolation and differentiation of stromal vascular cells to beige/brite cells. J Vis Exp. 2013;73:e50191.
29.
Hausman DB, Park HJ, Hausman GJ. Isolation and culture of preadipocytes from rodent white adipose tissue. Methods Mol Biol. 2008;456:201–19.PubMedCrossRef
30.
31.
Rizzatti V, Boschi F, Pedrotti M, Zoico E, Sbarbati A, Zamboni M. Lipid droplets characterization in adipocyte differentiated 3T3-L1 cells: size and optical density distribution. Eur J Histochem. 2013;57: e24.PubMedPubMedCentralCrossRef
32.
Anusree SS, Sindhu G, Preetha Rani MR, Raghu KG. Insulin resistance in 3T3-L1 adipocytes by TNF-α is improved by punicic acid through upregulation of insulin signalling pathway and endocrine function, and downregulation of proinflammatory cytokines. Biochimie. 2018;146:79–86.PubMedCrossRef
33.
Vishwanath D, Srinivasan H, Patil MS, Seetarama S, Agrawal SK, Dixit MN, et al. Novel method to differentiate 3T3 L1 cells in vitro to produce highly sensitive adipocytes for a GLUT4 mediated glucose uptake using fluorescent glucose analog. J Cell Commun Signal. 2013;7:129–40.PubMedPubMedCentralCrossRef
34.
Wang AJ, Yang Z. IL-25 or IL-17E protects against high-fat diet-induced hepatic steatosis in mice dependent upon IL-13 activation of STAT6. J Immunol. 2015;195:4771–80.PubMedCrossRef
35.
Armani A, Mammi C, Marzolla V, Calanchini M, Antelmi A, Rosano GM, et al. Cellular models for understanding adipogenesis, adipose dysfunction, and obesity. J Cell Biochem. 2010;110:564–72.PubMedCrossRef
36.
Ruiz-Ojeda FJ, Rupérez AI, Gomez-Llorente C, Gil A, Aguilera CM. Cell models and their application for studying adipogenic differentiation in relation to obesity: a review. Int J Mol Sci. 2016;17:1040.PubMedCentralCrossRef
37.
38.
Rickel EA, Siegel LA, Yoon BR, Rottman JB, Kugler DG, Swart DA, et al. Identification of functional roles for both IL-17RB and IL-17RA in mediating IL-25-induced activities. J Immunol. 2008;181:4299–310.PubMedCrossRef
39.
Kai Y, Gao J, Liu H, Wang Y, Tian C, Guo S, et al. Effects of IL-33 on 3T3-L1 cells and obese mice models induced by a high-fat diet. Int Immunopharmacol. 2021;101: 108209.PubMedCrossRef
40.
Lehr S, Hartwig S, Sell H. Adipokines: a treasure trove for the discovery of biomarkers for metabolic disorders. Proteomics Clin Appl. 2012;6:91–101.PubMedCrossRef
41.
Fu Y, Luo N, Klein RL, Garvey WT. Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. J Lipid Res. 2005;46:1369–79.PubMedCrossRef
42.
43.
Picó C, Palou M, Pomar CA, Rodríguez AM, Palou A. Leptin as a key regulator of the adipose organ. Rev Endocr Metab Disord. 2022;23:13–30.PubMedCrossRef
44.
Wang W, Fan YQ, Lv Z, Yao XJ, Wang W, Huang KW, et al. Interleukin-25 promotes basic fibroblast growth factor expression by human endothelial cells through interaction with IL-17RB, but not IL-17RA. Clin Exp Allergy. 2012;42:1604–14.PubMedCrossRef
45.
Huang P, Li Y, Lv Z, Wang J, Zhang Q, Yao X, et al. Comprehensive attenuation of IL-25-induced airway hyperresponsiveness, inflammation and remodelling by the PI3K inhibitor LY294002. Respirology. 2017;22:78–85.PubMedCrossRef
46.
47.
Quintero-Fabián S, Ortuño-Sahagún D, Vázquez-Carrera M, López-Roa RI. Alliin, a garlic (Allium sativum) compound, prevents LPS-induced inflammation in 3T3-L1 adipocytes. Mediators Inflamm. 2013;2013: 381815.PubMedPubMedCentralCrossRef
48.
Ajuwon KM, Spurlock ME. Adiponectin inhibits LPS-induced NF-kappaB activation and IL-6 production and increases PPARgamma2 expression in adipocytes. Am J Physiol Regul Integr Comp Physiol. 2005;288:R1220–5.PubMedCrossRef
49.
Zoico E, Garbin U, Olioso D, Mazzali G, Fratta Pasini AM, Di Francesco V, et al. The effects of adiponectin on interleukin-6 and MCP-1 secretion in lipopolysaccharide-treated 3T3-L1 adipocytes: role of the NF-kappaB pathway. Int J Mol Med. 2009;24:847–51.PubMedCrossRef
50.
Lira FS, Rosa JC, Pimentel GD, Seelaender M, Damaso AR, Oyama LM, et al. Both adiponectin and interleukin-10 inhibit LPS-induced activation of the NF-κB pathway in 3T3-L1 adipocytes. Cytokine. 2012;57:98–106.PubMedCrossRef
51.
Tourniaire F, Romier-Crouzet B, Lee JH, Marcotorchino J, Gouranton E, Salles J, et al. Chemokine expression in inflamed adipose tissue is mainly mediated by NF-κB. PLoS ONE. 2013;8: e66515.PubMedPubMedCentralCrossRef
52.
Stern JH, Rutkowski JM, Scherer PE. Adiponectin, leptin, and fatty acids in the maintenance of metabolic homeostasis through adipose tissue crosstalk. Cell Metab. 2016;23:770–84.PubMedPubMedCentralCrossRef
53.
Al-Mansoori L, Al-Jaber H, Prince MS, Elrayess MA. Role of inflammatory cytokines, growth factors and adipokines in adipogenesis and insulin resistance. Inflammation. 2022;45:31–44.PubMedCrossRef
54.
Shinjo T, Iwashita M, Yamashita A, Sano T, Tsuruta M, Matsunaga H, et al. IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2016;477:241–6.PubMedCrossRef
55.
Teijeiro A, Garrido A, Ferre A, Perna C, Djouder N. Inhibition of the IL-17A axis in adipocytes suppresses diet-induced obesity and metabolic disorders in mice. Nat Metab. 2021;3:496–512.PubMedCrossRef
56.
Zeyda M, Wernly B, Demyanets S, Kaun C, Hämmerle M, Hantusch B, et al. Severe obesity increases adipose tissue expression of interleukin-33 and its receptor ST2, both predominantly detectable in endothelial cells of human adipose tissue. Int J Obes (Lond). 2013;37:658–65.CrossRef
57.
Pereira RI, Draznin B. Inhibition of the phosphatidylinositol 3’-kinase signaling pathway leads to decreased insulin-stimulated adiponectin secretion from 3T3-L1 adipocytes. Metabolism. 2005;54:1636–43.PubMedCrossRef
58.
Cong L, Chen K, Li J, Gao P, Li Q, Mi S, et al. Regulation of adiponectin and leptin secretion and expression by insulin through a PI3K-PDE3B dependent mechanism in rat primary adipocytes. Biochem J. 2007;403:519–25.PubMedPubMedCentralCrossRef
59.
Caruso R, Stolfi C, Sarra M, Rizzo A, Fantini MC, Pallone F, et al. Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase-dependent induction of Socs-3. Blood. 2009;113:3512–9.PubMedCrossRef
60.
Chirumbolo S, Franceschetti G, Zoico E, Bambace C, Cominacini L, Zamboni M. LPS response pattern of inflammatory adipokines in an in vitro 3T3-L1 murine adipocyte model. Inflamm Res. 2014;63:495–507.PubMedCrossRef
61.
Keophiphath M, Rouault C, Divoux A, Clément K, Lacasa D. CCL5 promotes macrophage recruitment and survival in human adipose tissue. Arterioscler Thromb Vasc Biol. 2010;30:39–45.PubMedCrossRef
62.
Digby JE, McNeill E, Dyar OJ, Lam V, Greaves DR, Choudhury RP. Anti-inflammatory effects of nicotinic acid in adipocytes demonstrated by suppression of fractalkine, RANTES, and MCP-1 and upregulation of adiponectin. Atherosclerosis. 2010;209:89–95.PubMedPubMedCentralCrossRef
63.
Wu H, Ghosh S, Perrard XD, Feng L, Garcia GE, Perrard JL, et al. T-cell accumulation and regulated on activation, normal T cell expressed and secreted upregulation in adipose tissue in obesity. Circulation. 2007;115:1029–38.PubMedCrossRef
64.
Stefan N, Stumvoll M. Adiponectin–its role in metabolism and beyond. Horm Metab Res. 2002;34:469–74.PubMedCrossRef
65.
Masaie H, Oritani K, Yokota T, Takahashi I, Shirogane T, Ujiie H, et al. Adiponectin binds to chemokines via the globular head and modulates interactions between chemokines and heparan sulfates. Exp Hematol. 2007;35:947–56.PubMedCrossRef
Metadata
Title
IL-25 directly modulates adipocyte function and inflammation through the regulation of adiponectin
Authors
Siranart Jeerawattanawart
Pilaiwan Siripurkpong
Sittiruk Roytrakul
Pornpimon Angkasekwinai
Publication date
12-07-2022
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 10-11/2022
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-022-01606-x

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