Abstract
The murine dorsal air pouch model is a valuable tool for studying acute peripheral inflammatory reactions. We used this model to study the effect of diet on the onset of acute inflammation. Mice were fed a normal or a high-fat diet (HFD) for 5 weeks. Air pouches were raised and injected with non-stimulating (saline) or stimulating solution (saline containing lipopolysaccharides). After 4 h, leukocytes in the pouch fluid were enumerated, sorted and their viability measured. Cytokine/chemokine levels in the cell-free fluid were measured using a cytometric bead assay. Gene expression level was measured in leukocytes and in lining tissues using comparative real-time PCR. Leukocyte migration and cytokine/chemokine secretion were decreased substantially in mice fed the HFD. In contrast, leptin levels were elevated. Gene expression profiles in leukocytes recovered from the pouch and in the pouch-lining tissue (believed to have an important role in the initiation of granulocyte recruitment) were depressed. Genes encoding CC and CXC family chemokines were among the most negatively affected. These results suggest that a HFD can alter peripheral tissue activation as well as leukocyte recruitment and response, thereby affecting the development of an effective local immune response, which could have deleterious consequences.
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References
Swindell WR, Johnston A, Gudjonsson JE . Transcriptional profiles of leukocyte populations provide a tool for interpreting gene expression patterns associated with high fat diet in mice. PLoS One 2010; 5: e11861.
Lindholm CR, Ertel RL, Bauwens JD, Schmuck EG, Mulligan JD, Saupe KW . A high-fat diet decreases AMPK activity in multiple tissues in the absence of hyperglycemia or systemic inflammation in rats. J Physiol Biochem 2013; 69: 165–175.
Strandberg L, Verdrengh M, Enge M, Andersson N, Amu S, Onnheim K et al. Mice chronically fed high-fat diet have increased mortality and disturbed immune response in sepsis. PLoS One 2009; 4: e7605.
Fellmann L, Nascimento AR, Tibirica E, Bousquet P . Murine models for pharmacological studies of the metabolic syndrome. Pharmacol Ther 2013; 137: 331–340.
Weisberg SP, Hunter D, Huber R, Lemieux J, Slaymaker S, Vaddi K et al. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J Clin Invest 2006; 116: 115–124.
McColl SR, St-Onge M, Dussault AA, Laflamme C, Bouchard L, Boulanger J et al. Immunomodulatory impact of the A2A adenosine receptor on the profile of chemokines produced by neutrophils. FASEB J 2006; 20: 187–189.
Iida M, Watanabe K, Tsurufuji M, Takaishi K, Iizuka Y, Tsurufuji S . Level of neutrophil chemotactic factor CINC/gro, a member of the interleukin-8 family, associated with lipopolysaccharide-induced inflammation in rats. Infect Immun 1992; 60: 1268–1272.
Ribeiro RA, Flores CA, Cunha FQ, Ferreira SH . IL-8 causes in vivo neutrophil migration by a cell-dependent mechanism. Immunology 1991; 73: 472–477.
Garcia-Ramallo E, Marques T, Prats N, Beleta J, Kunkel SL, Godessart N . Resident cell chemokine expression serves as the major mechanism for leukocyte recruitment during local inflammation. J Immunol 2002; 169: 6467–6473.
Takano K, Nakagawa H . Contribution of cytokine-induced neutrophil chemoattractant CINC-2 and CINC-3 to neutrophil recruitment in lipopolysaccharide-induced inflammation in rats. Inflamm Res 2001; 50: 503–508.
Tanabe J, Watanabe M, Mue S, Ohuchi K . Leukocyte-derived neutrophil chemotactic factor-2 produced by infiltrated leukocytes in allergic inflammation model in rats is macrophage inflammatory protein-2. Immunol Invest 1995; 24: 757–764.
Ramos CD, Heluy-Neto NE, Ribeiro RA, Ferreira SH, Cunha FQ . Neutrophil migration induced by IL-8-activated mast cells is mediated by CINC-1. Cytokine 2003; 21: 214–223.
Zhang XW, Wang Y, Liu Q, Thorlacius H . Redundant function of macrophage inflammatory protein-2 and KC in tumor necrosis factor-alpha-induced extravasation of neutrophils in vivo. Eur J Pharmacol 2001; 427: 277–283.
Shibata F, Konishi K, Kato H, Komorita N, al-Mokdad M, Fujioka M et al. Recombinant production and biological properties of rat cytokine-induced neutrophil chemoattractants, GRO/CINC-2 alpha, CINC-2 beta and CINC-3. Eur J Biochem 1995; 231: 306–311.
Panchal SK, Brown L . Rodent models for metabolic syndrome research. J Biomed Biotechnol 2011; 2011: 351982.
Enos RT, Davis JM, Velazquez KT, McClellan JL, Day SD, Carnevale KA et al. Influence of dietary saturated fat content on adiposity, macrophage behavior, inflammation, and metabolism: composition matters. J Lipid Res 2013; 54: 152–163.
Ghibaudi L, Cook J, Farley C, van Heek M, Hwa JJ . Fat intake affects adiposity, comorbidity factors, and energy metabolism of Sprague-Dawley rats. Obes Res 2002; 10: 956–963.
St-Onge M, Dumas A, Michaud A, Laflamme C, Dussault AA, Pouliot M . Impact of anti-inflammatory agents on the gene expression profile of stimulated human neutrophils: unraveling endogenous resolution pathways. PLoS One 2009; 4: e4902.
Kassi E, Pervanidou P, Kaltsas G, Chrousos G . Metabolic syndrome: definitions and controversies. BMC Med 2011; 9: 48.
Ervin RB . Prevalence of metabolic syndrome among adults 20 years of age and over, by sex, age, race and ethnicity, and body mass index: United States, 2003-2006. National Health Stat Rep 2009;, (13): 1–7. Available at http://www.cdc.gov/nchs/data/nhsr/nhsr013.pdf.
Edwards JC, Sedgwick AD, Willoughby DA . The formation of a structure with the features of synovial lining by subcutaneous injection of air: an in vivo tissue culture system. The J Pathol 1981; 134: 147–156.
Colobran R, Pujol-Borrell R, Armengol MP, Juan M . The chemokine network. I. How the genomic organization of chemokines contains clues for deciphering their functional complexity. Clin Exp Immunol 2007; 148: 208–217.
Heyninck K, Beyaert R . A20 inhibits NF-kappaB activation by dual ubiquitin-editing functions. Trends Biochem Sci 2005; 30: 1–4.
Huang CY, Tan TH . DUSPs, to MAP kinases and beyond. Cell Biosci 2012; 2: 24.
Yoshimura A, Suzuki M, Sakaguchi R, Hanada T, Yasukawa H . SOCS, inflammation, and autoimmunity. Front Immunol 2012; 3: 20.
McMorrow JP, Murphy EP . Inflammation: a role for NR4A orphan nuclear receptors? Biochem Soc Trans 2011; 39: 688–693.
Harvey J, Ashford ML . Leptin in the CNS: much more than a satiety signal. Neuropharmacology 2003; 44: 845–854.
Ceddia RB, Koistinen HA, Zierath JR, Sweeney G . Analysis of paradoxical observations on the association between leptin and insulin resistance. FASEB J 2002; 16: 1163–1176.
Fruhbeck G . Intracellular signalling pathways activated by leptin. Biochem J 2006; 393 (Pt 1): 7–20.
Caldefie-Chezet F, Poulin A, Tridon A, Sion B, Vasson MP . Leptin: a potential regulator of polymorphonuclear neutrophil bactericidal action? J Leukoc Biol 2001; 69: 414–418.
Faggioni R, Feingold KR, Grunfeld C . Leptin regulation of the immune response and the immunodeficiency of malnutrition. FASEB J 2001; 15: 2565–2571.
Caldefie-Chezet F, Poulin A, Vasson MP . Leptin regulates functional capacities of polymorphonuclear neutrophils. Free Radic Res 2003; 37: 809–814.
Ottonello L, Gnerre P, Bertolotto M, Mancini M, Dapino P, Russo R et al. Leptin as a uremic toxin interferes with neutrophil chemotaxis. J Am Soc Nephrol 2004; 15: 2366–2372.
Moore SI, Huffnagle GB, Chen GH, White ES, Mancuso P . Leptin modulates neutrophil phagocytosis of Klebsiella pneumoniae. Infect Immun 2003; 71: 4182–4185.
Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS . TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 2006; 116: 3015–3025.
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: 1821–1830.
Henrichot E, Juge-Aubry CE, Pernin A, Pache JC, Velebit V, Dayer JM et al. Production of chemokines by perivascular adipose tissue: a role in the pathogenesis of atherosclerosis? Arterioscler Thromb Vasc Biol 2005; 25: 2594–2599.
Hagita S, Osaka M, Shimokado K, Yoshida M . Adipose inflammation initiates recruitment of leukocytes to mouse femoral artery: role of adipo-vascular axis in chronic inflammation. PLoS One 2011; 6: e19871.
Frohlich M, Imhof A, Berg G, Hutchinson WL, Pepys MB, Boeing H et al. Association between C-reactive protein and features of the metabolic syndrome: a population-based study. Diabetes Care 2000; 23: 1835–1839.
Zambon A, Pauletto P, Crepaldi G . Review article: the metabolic syndrome–a chronic cardiovascular inflammatory condition. Aliment Pharmacol Ther 2005; 22 (Suppl 2): 20–23.
Talukdar S, Oh da Y, Bandyopadhyay G, Li D, Xu J, McNelis J et al. Neutrophils mediate insulin resistance in mice fed a high-fat diet through secreted elastase. Nat Med 2012; 18: 1407–1412.
Boyum A . A one-stage procedure for isolation of granulocytes and lymphocytes from human blood. General sedimentation properties of white blood cells in a 1 g gravity field. Scand J Clin Lab Invest Suppl 1968; 97: 51–76.
Pouliot M, Fiset ME, Masse M, Naccache PH, Borgeat P . Adenosine up-regulates cyclooxygenase-2 in human granulocytes: impact on the balance of eicosanoid generation. J Immunol 2002; 169: 5279–5286.
Dussault AA, Pouliot M . Rapid and simple comparison of messenger RNA levels using real-time PCR. Biol Procedures Online 2006; 8: 1–10.
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002; 3 research0034–research0034.11. doi:10.1186/gb-2002-3-7-research0034.
Andersen CL, Jensen JL, Orntoft TF . Normalization of real-time quantitative reverse transcription-PCR data: a model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 2004; 64: 5245–5250.
Pfaffl MW, Tichopad A, Prgomet C, Neuvians TP . Determination of stable housekeeping genes, differentially regulated target genes and sample integrity: BestKeeper—Excel-based tool using pair-wise correlations. Biotechnol Lett 2004; 26: 509–515.
Silver N, Best S, Jiang J, Thein SL . Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR. BMC Mol Biol 2006; 7: 33.
Radonic A, Thulke S, Mackay IM, Landt O, Siegert W, Nitsche A . Guideline to reference gene selection for quantitative real-time PCR. Biochem Biophys Res Commun 2004; 313: 856–862.
Zhang X, Ding L, Sandford AJ . Selection of reference genes for gene expression studies in human neutrophils by real-time PCR. BMC Mol Biol 2005; 6: 4.
Acknowledgements
This work was funded by grants from the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI) to MP (grant numbers MOP220733 and 19576, respectively). GB-M is the recipient of a studentship from the Wilbrod-Bherer Foundation. MSG is the recipient of a post-doctoral fellowship from the Fonds de Recherche du Québec-Santé (FRQS). EB is the recipient of a scholarship from the FRQS.
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Laflamme, C., Bertheau-Mailhot, G., Giambelluca, M. et al. Evidence of impairment of normal inflammatory reaction by a high-fat diet. Genes Immun 15, 224–232 (2014). https://doi.org/10.1038/gene.2014.8
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DOI: https://doi.org/10.1038/gene.2014.8