Top

Published in:

01-01-2020 | Obesity | Note

Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

Authors: Rika Tsuhako, Hiroki Yoshida, Chihiro Sugita, Masahiko Kurokawa

Published in: Journal of Natural Medicines | Issue 1/2020

Abstract

Recruitment of immune cells to adipose tissue is altered dramatically in obesity, which results in chronic inflammation of the adipose tissue that leads to metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. The regulation of immune cell infiltration into adipose tissue has prophylactic and therapeutic implications for obesity-related diseases. We previously showed that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue by inhibiting monocyte chemoattractant protein-1 (MCP-1) expression in the progression phase to high-fat diet (HFD)-induced obesity. In the current study, we evaluated the effects of naringenin on neutrophil infiltration into adipose tissue, because neutrophils also infiltrate into adipose tissue in the progression phase to obesity. Naringenin suppressed neutrophil infiltration into adipose tissue induced by the short-term (2 weeks) feeding of a HFD to mice. Naringenin tended to inhibit the HFD-induced expression of several chemokines, including MCP-1 and MCP-3, in adipose tissue. Naringenin also inhibited MCP-3 expression in 3T3-L1 adipocytes and a co-culture of 3T3-L1 adipocytes and RAW264 macrophages. However, naringenin did not affect the expression of macrophage inflammatory protein-2 (MIP-2), an important chemokine for neutrophil migration and activation, in macrophages or in a co-culture of adipocytes and macrophages. Our results suggest that naringenin suppresses neutrophil infiltration into adipose tissue via the regulation of MCP-3 expression and macrophage infiltration.

Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830CrossRef

Balistreri CR, Caruso C, Candore G (2010) The role of adipose tissue and adipokines in obesity-related inflammatory diseases. Mediat Inflamm 2010:802078CrossRef

Surmi BK, Hasty AH (2010) The role of chemokines in recruitment of immune cells to the artery wall and adipose tissue. Vasc Pharmacol 52:27–36CrossRef

Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808CrossRef

Suganami T, Nishida J, Ogawa Y (2005) A paracrine loop between adipocytes and macrophages aggravates inflammatory changes: role of free fatty acids and tumor necrosis factor alpha. Arterioscler Thromb Vasc Biol 25:2062–2068CrossRef

Suganami T, Ogawa Y (2010) Adipose tissue macrophages: their role in adipose tissue remodeling. J Leukoc Biol 88:33–39CrossRef

Elgazar-Carmon V, Rudich A, Hadad N, Levy R (2008) Neutrophils transiently infiltrate intra-abdominal fat early in the course of high-fat feeding. J Lipid Res 49:1894–1903CrossRef

Talukdar S, Oh DY, Bandyopadhyay G, Li D, Xu J, McNelis J, Lu M, Li P, Yan Q, Zhu Y, Ofrecio J, Lin M, Brenner MB, Olefsky JM (2012) Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 18:1407–1412CrossRef

Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, Fischer-Posovszky P, Barth TF, Dragun D, Skurk T, Hauner H, Bluher M, Unger T, Wolf AM, Knippschild U, Hombach V, Marx N (2008) T-lymphocyte infiltration in visceral adipose tissue: a primary event in adipose tissue inflammation and the development of obesity-mediated insulin resistance. Arterioscler Thromb Vasc Biol 28:1304–1310CrossRef

10.

Nishimura S, Manabe I, Nagasaki M, Eto K, Yamashita H, Ohsugi M, Otsu M, Hara K, Ueki K, Sugiura S, Yoshimura K, Kadowaki T, Nagai R (2009) CD8⁺effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15:914–920CrossRef

11.

Salehi B, Fokou PVT, Sharifi-Rad M, Zucca P, Pezzani R, Martins N, Sharifi-Rad J (2019) The therapeutic potential of naringenin: a review of clinical trials. Pharm (Basel) 12:11CrossRef

12.

Kim TH, Kim GD, Ahn HJ, Cho JJ, Park YS, Park CS (2013) The inhibitory effect of naringenin on atopic dermatitis induced by DNFB in NC/Nga mice. Life Sci 93:516–524CrossRef

13.

Wang J, Qi Y, Niu X, Tang H, Meydani SN, Wu D (2018) Dietary naringenin supplementation attenuates experimental autoimmune encephalomyelitis by modulating autoimmune inflammatory responses in mice. J Nutr Biochem 54:130–139CrossRef

14.

Pinho-Ribeiro FA, Zarpelon AC, Mizokami SS, Borghi SM, Bordignon J, Silva RL, Cunha TM, Alves-Filho JC, Cunha FQ, Casagrande R, Verri WA Jr (2016) The citrus flavonone naringenin reduces lipopolysaccharide-induced inflammatory pain and leukocyte recruitment by inhibiting NF-kappaB activation. J Nutr Biochem 33:8–14CrossRef

15.

Zhao M, Li C, Shen F, Wang M, Jia N, Wang C (2017) Naringenin ameliorates LPS-induced acute lung injury through its anti-oxidative and anti-inflammatory activity and by inhibition of the PI3 K/Akt pathway. Exp Ther Med 14:2228–2234CrossRef

16.

Yoshida H, Takamura N, Shuto T, Ogata K, Tokunaga J, Kawai K, Kai H (2010) The citrus flavonoids hesperetin and naringenin block the lipolytic actions of TNF-alpha in mouse adipocytes. Biochem Biophys Res Commun 394:728–732CrossRef

17.

Yoshida H, Watanabe W, Oomagari H, Tsuruta E, Shida M, Kurokawa M (2013) Citrus flavonoid naringenin inhibits TLR2 expression in adipocytes. J Nutr Biochem 24:1276–1284CrossRef

18.

Yoshida H, Watanabe H, Ishida A, Watanabe W, Narumi K, Atsumi T, Sugita C, Kurokawa M (2014) Naringenin suppresses macrophage infiltration into adipose tissue in an early phase of high-fat diet-induced obesity. Biochem Biophys Res Commun 454:95–101CrossRef

19.

Bertola A, Ciucci T, Rousseau D, Bourlier V, Duffaut C, Bonnafous S, Blin-Wakkach C, Anty R, Iannelli A, Gugenheim J, Tran A, Bouloumie A, Gual P, Wakkach A (2012) Identification of adipose tissue dendritic cells correlated with obesity-associated insulin-resistance and inducing Th17 responses in mice and patients. Diabetes 61:2238–2247CrossRef

20.

Jiao P, Chen Q, Shah S, Du J, Tao B, Tzameli I, Yan W, Xu H (2009) Obesity-related upregulation of monocyte chemotactic factors in adipocytes: involvement of nuclear factor-kappaB and c-Jun NH2-terminal kinase pathways. Diabetes 58:104–115CrossRef

21.

Xu LL, McVicar DW, Ben-Baruch A, Kuhns DB, Johnston J, Oppenheim JJ, Wang JM (1995) Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils. Eur J Immunol 25:2612–2617CrossRef

22.

Struyf S, Gouwy M, Dillen C, Proost P, Opdenakker G, Van Damme J (2005) Chemokines synergize in the recruitment of circulating neutrophils into inflamed tissue. Eur J Immunol 35:1583–1591CrossRef

23.

De Filippo K, Dudeck A, Hasenberg M, Nye E, van Rooijen N, Hartmann K, Gunzer M, Roers A, Hogg N (2013) Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood 121:4930–4937CrossRef

24.

Schiwon M, Weisheit C, Franken L, Gutweiler S, Dixit A, Meyer-Schwesinger C, Pohl JM, Maurice NJ, Thiebes S, Lorenz K, Quast T, Fuhrmann M, Baumgarten G, Lohse MJ, Opdenakker G, Bernhagen J, Bucala R, Panzer U, Kolanus W, Grone HJ, Garbi N, Kastenmuller W, Knolle PA, Kurts C, Engel DR (2014) Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium. Cell 156:456–468CrossRef

25.

Kim ND, Luster AD (2015) The role of tissue resident cells in neutrophil recruitment. Trends Immunol 36:547–555CrossRef

26.

Qin CC, Liu YN, Hu Y, Yang Y, Chen Z (2017) Macrophage inflammatory protein-2 as mediator of inflammation in acute liver injury. World J Gastroenterol 23:3043–3052CrossRef

27.

Hamalainen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E (2007) Anti-inflammatory effects of flavonoids: genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-kappaB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF-kappaB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediat Inflamm 2007:45673CrossRef

28.

Shi D, Xu Y, Du X, Chen X, Zhang X, Lou J, Li M, Zhuo J (2015) Co-treatment of THP-1 cells with naringenin and curcumin induces cell cycle arrest and apoptosis via numerous pathways. Mol Med Rep 12:8223–8228CrossRef

29.

Park JH, Jin CY, Lee BK, Kim GY, Choi YH, Jeong YK (2008) Naringenin induces apoptosis through downregulation of Akt and caspase-3 activation in human leukemia THP-1 cells. Food Chem Toxicol 46:3684–3690CrossRef

30.

Lee BC, Lee J (2014) Cellular and molecular players in adipose tissue inflammation in the development of obesity-induced insulin resistance. Biochim Biophys Acta 1842:446–462CrossRef

31.

Siedle B, Hrenn A, Merfort I (2007) Natural compounds as inhibitors of human neutrophil elastase. Planta Med 73:401–420CrossRef

32.

Melzig MF, Loser B, Ciesielski S (2001) Inhibition of neutrophil elastase activity by phenolic compounds from plants. Pharmazie 56:967–970PubMed

Title: Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice
Authors: Rika Tsuhako
Hiroki Yoshida
Chihiro Sugita
Masahiko Kurokawa
Publication date: 01-01-2020
Publisher: Springer Singapore
Keywords: Obesity
Obesity
Published in: Journal of Natural Medicines / Issue 1/2020
Print ISSN: 1340-3443
Electronic ISSN: 1861-0293
DOI: https://doi.org/10.1007/s11418-019-01332-5

At a glance: The STEP trials

Springer Medicine

Naringenin suppresses neutrophil infiltration into adipose tissue in high-fat diet-induced obese mice

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2020

Consumption of lycopene-rich tomatoes improved glucose homeostasis in rats via an increase in leptin levels

Chemical constituents from Ginkgo biloba leaves and their cytotoxicity activity

DNA barcoding for identification of agarwood source species using trnL-trnF and matK DNA sequences

Metabolomic profiling of Saposhnikoviae Radix from Mongolia by LC–IT–TOF–MS/MS and multivariate statistical analysis

Four new cucurbitane-type triterpenes from Momordica charantia L. with their cytotoxic activities and protective effects on H2O2-damaged pancreatic cells

Selective cytotoxicity of epidithiodiketopiperazine DC1149B, produced by marine-derived Trichoderma lixii on the cancer cells adapted to glucose starvation