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04.06.2019 | Original Contribution

High-fat diet induced central adiposity (visceral fat) is associated with increased fibrosis and decreased immune cellularity of the mesenteric lymph node in mice

verfasst von: Aaron M. Magnuson, Daniel P. Regan, Andrea D. Booth, Josephine K. Fouts, Claudia M. Solt, Jessica L. Hill, Steve W. Dow, Michelle T. Foster

Erschienen in: European Journal of Nutrition | Ausgabe 4/2020

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Abstract

Purpose

Accumulation of visceral, but not subcutaneous, adipose tissue is highly associated with metabolic disease. Inflammation inciting from adipose tissue is commonly associated with metabolic disease risk and comorbidities. However, constituents of the immune system, lymph nodes, embedded within these adipose depots remain under-investigated. We hypothesize that, lymph nodes are inherently distinct and differentially respond to diet-induced obesity much like the adipose depots they reside in.

Methods

Adipose tissue and lymph nodes were collected from the visceral and inguinal depots of male mice fed 13 weeks of standard CHOW or high fat diet (HFD). Immune cells were isolated from tissues, counted and characterized by flow cytometry or plated for proliferative capacity following Concanavalin A stimulation. Lymph node size and fibrosis area were also characterized.

Results

In HFD fed mice visceral adipose tissue accumulation was associated with significant enlargement of the lymph node encased within. The subcutaneous lymph node did not change. Compared with mice fed CHOW for 13 weeks, mice fed HFD had a decline in immune cell populations and immune cell proliferative ability, as well as, exacerbated fibrosis accumulation, within the visceral, but not subcutaneous, lymph node.

Conclusions

Obesity-induced chronic low-grade inflammation is associated with impaired immunity and increased susceptibility to disease. Excessive visceral adiposity and associated inflammation driven by diet likely leads to obesity-induced immune suppression by way of lymph node/lymphatic system pathophysiology.

Lafontan M, Berlan M (2003) Do regional differences in adipocyte biology provide new pathophysiological insights? Trends Pharmacol Sci 24(6):276–283. https://doi.org/10.1016/S0165-6147(03)00132-9 CrossRefPubMed

Harman-Boehm I, Blüher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E, Shai I, Klöting N, Stumvoll M, Bashan N, Rudich A (2007) Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92(6):2240–2247. https://doi.org/10.1210/jc.2006-1811 CrossRefPubMed

Mraz M, Haluzik M (2014) The role of adipose tissue immune cells in obesity and low-grade inflammation. J Endocrinol 222(3):R113–R127. https://doi.org/10.1530/joe-14-0283 CrossRefPubMed

Blüher M (2013) Adipose tissue dysfunction contributes to obesity related metabolic diseases. Best Pract Res Clin Endocrinol Metab 27(2):163–177. https://doi.org/10.1016/j.beem.2013.02.005 CrossRefPubMed

Neeland IJ, Ayers CR, Rohatgi AK, Turer AT, Berry JD, Das SR, Vega GL, Khera A, McGuire DK, Grundy SM, de Lemos JA (2013) Associations of visceral and abdominal subcutaneous adipose tissue with markers of cardiac and metabolic risk in obese adults. Obesity 21(9):E439–E447. https://doi.org/10.1002/oby.20135 CrossRefPubMed

Goossens GH (2017) The metabolic phenotype in obesity: fat mass, body fat distribution, and adipose tissue function. Obes Facts 10(3):207–215CrossRef

Esser N, Legrand-Poels S, Piette J, Scheen AJ, Paquot N (2014) Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 105(2):141–150. https://doi.org/10.1016/j.diabres.2014.04.006 CrossRefPubMed

Kintscher U, Hartge M, Hess K, Foryst-Ludwig A, Clemenz M, Wabitsch M, Fischer-Posovszky P, Barth TFE, Dragun D, Skurk T, Hauner H, Blüher M, Unger T, Wolf A-M, 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(7):1304–1310. https://doi.org/10.1161/atvbaha.108.165100 CrossRefPubMed

Ibrahim MM (2010) Subcutaneous and visceral adipose tissue: structural and functional differences. Obes Rev 11(1):11–18. https://doi.org/10.1111/j.1467-789X.2009.00623.x CrossRefPubMed

10.

Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, Caruso C (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immunity Ageing 2(1):8. https://doi.org/10.1186/1742-4933-2-8 CrossRefPubMed

11.

Willard-Mack CL (2006) Normal structure, function, and histology of lymph nodes. Toxicol Pathol 34(5):409–424. https://doi.org/10.1080/01926230600867727 CrossRefPubMed

12.

Yoffey JM, Courtice FC (1970) Lymphatics, lymph and the lymphomyeloid complex. Academic Press, London

13.

Weitman ES, Aschen SZ, Farias-Eisner G, Albano N, Cuzzone DA, Ghanta S, Zampell JC, Thorek D, Mehrara BJ (2013) Obesity impairs lymphatic fluid transport and dendritic cell migration to lymph nodes. PLoS One 8(8):e70703. https://doi.org/10.1371/journal.pone.0070703 CrossRefPubMedPubMedCentral

14.

Arngrim N, Simonsen L, Holst JJ, Bulow J (2013) Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation[quest]. Int J Obes 37(5):748–750. https://doi.org/10.1038/ijo.2012.98 CrossRef

15.

von der Weid PY, Rainey KJ (2010) Review article: lymphatic system and associated adipose tissue in the development of inflammatory bowel disease. Aliment Pharmacol Ther 32(6):697–711. https://doi.org/10.1111/j.1365-2036.2010.04407.x CrossRefPubMed

16.

Magnuson A, Regan D, Fouts J, Booth A, Dow S, Foster M (2017) Diet-induced obesity causes visceral, but not subcutaneous, lymph node hyperplasia via increases in specific immune cell populations. Cell Prolif 50:5CrossRef

17.

Soderberg KA, Payne GW, Sato A, Medzhitov R, Segal SS, Iwasaki A (2005) Innate control of adaptive immunity via remodeling of lymph node feed arteriole. Proc Natl Acad Sci USA 102(45):16315–16320. https://doi.org/10.1073/pnas.0506190102 CrossRefPubMed

18.

Kim CS, Lee SC, Kim YM, Kim BS, Choi HS, Kawada T, Kwon BS, Yu R (2008) Visceral fat accumulation induced by a high-fat diet causes the atrophy of mesenteric lymph nodes in obese mice. Obesity 16(6):1261–1269. https://doi.org/10.1038/oby.2008.55 CrossRefPubMed

19.

Cavalera M, Wang J, Frangogiannis NG (2014) Obesity, metabolic dysfunction, and cardiac fibrosis: pathophysiological pathways, molecular mechanisms, and therapeutic opportunities. Transl Res 164(4):323–335. https://doi.org/10.1016/j.trsl.2014.05.001 CrossRefPubMedPubMedCentral

20.

Eschalier R, Rossignol P, Kearney-Schwartz A, Adamopoulos C, Karatzidou K, Fay R, Mandry D, Marie PY, Zannad F (2014) Features of cardiac remodeling, associated with blood pressure and fibrosis biomarkers, are frequent in subjects with abdominal obesity. Hypertension (Dallas, Tex: 1979) 63(4):740–746. https://doi.org/10.1161/hypertensionaha.113.02419 CrossRef

21.

Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I, Khalil L, Turpin G, Opolon P, Poynard T (2000) Liver fibrosis in overweight patients. Gastroenterology 118(6):1117–1123CrossRef

22.

Sharma K (2014) Obesity, oxidative stress, and fibrosis in chronic kidney disease. Kidney Int Suppl 4(1):113–117. https://doi.org/10.1038/kisup.2014.21 CrossRef

23.

Sun K, Kusminski CM, Scherer PE (2011) Adipose tissue remodeling and obesity. J Clin Investig 121(6):2094CrossRef

24.

O’neill S, O’driscoll L (2015) Metabolic syndrome: a closer look at the growing epidemic and its associated pathologies. Obes Rev 16(1):1–12CrossRef

25.

Björntorp P (1991) Metabolic implications of body fat distribution. Diabetes Care 14(12):1132–1143CrossRef

26.

De Pergola G, Silvestris F (2013) Obesity as a major risk factor for cancer. J Obes 2013:291546. https://doi.org/10.1155/2013/291546 CrossRefPubMedPubMedCentral

27.

Bilecik NA, Tuna S, Samancı N, Balcı N, Akbaş H (2014) Prevalence of metabolic syndrome in women with rheumatoid arthritis and effective factors. Int J Clin Exp Med 7(8):2258–2265PubMed

28.

Lee CG, Lee JK, Kang Y-S, Shin S, Kim JH, Lim YJ, Koh M-S, Lee JH, Kang HW (2015) Visceral abdominal obesity is associated with an increased risk of irritable bowel syndrome. Am J Gastroenterol 110(2):310CrossRef

29.

Kuk JL, Katzmarzyk PT, Nichaman MZ, Church TS, Blair SN, Ross R (2006) Visceral fat is an independent predictor of all-cause mortality in men. Obesity 14(2):336–341CrossRef

30.

Halberg N, Khan T, Trujillo ME, Wernstedt-Asterholm I, Attie AD, Sherwani S, Wang ZV, Landskroner-Eiger S, Dineen S, Magalang UJ, Brekken RA, Scherer PE (2009) Hypoxia-inducible factor 1α induces fibrosis and insulin resistance in white adipose tissue. Mol Cell Biol 29(16):4467–4483. https://doi.org/10.1128/mcb.00192-09 CrossRefPubMedPubMedCentral

31.

Ye J, Gao Z, Yin J, He Q (2007) Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 293(4):E1118–E1128. https://doi.org/10.1152/ajpendo.00435.2007 CrossRefPubMed

32.

Hosogai N, Fukuhara A, Oshima K, Miyata Y, Tanaka S, Segawa K, Furukawa S, Tochino Y, Komuro R, Matsuda M, Shimomura I (2007) Adipose tissue hypoxia in obesity and its impact on adipocytokine dysregulation. Diabetes 56(4):901–911. https://doi.org/10.2337/db06-0911 CrossRefPubMed

33.

Schacker TW, Brenchley JM, Beilman GJ, Reilly C, Pambuccian SE, Taylor J, Skarda D, Larson M, Douek DC, Haase AT (2006) Lymphatic tissue fibrosis is associated with reduced numbers of naive CD4+ T cells in human immunodeficiency virus type 1 infection. Clin Vaccine Immunol 13(5):556–560CrossRef

34.

Paiardini M, Muller-Trutwin M (2013) HIV-associated chronic immune activation. Immunol Rev 254(1):78–101. https://doi.org/10.1111/imr.12079 CrossRefPubMedPubMedCentral

35.

Niu N, Qin X (2013) New insights into IL-7 signaling pathways during early and late T cell development. Cell Mol Immunol 10(3):187–189. https://doi.org/10.1038/cmi.2013.11 CrossRefPubMedPubMedCentral

36.

Brown FD, Turley SJ (2015) Fibroblastic reticular cells: organization and regulation of the T lymphocyte life cycle. J Immunol 194(4):1389–1394. https://doi.org/10.4049/jimmunol.1402520 CrossRefPubMedPubMedCentral

37.

Kvietys PR, Specian RD, Grisham MB, Tso P (1991) Jejunal mucosal injury and restitution: role of hydrolytic products of food digestion. Am J Physiol 261(3 Pt 1):G384–G391PubMed

38.

Ding S, Chi MM, Scull BP, Rigby R, Schwerbrock NM, Magness S, Jobin C, Lund PK (2010) High-fat diet: bacteria interactions promote intestinal inflammation which precedes and correlates with obesity and insulin resistance in mouse. PLoS One 5(8):e12191. https://doi.org/10.1371/journal.pone.0012191 CrossRefPubMedPubMedCentral

39.

Novotny Nunez I, Maldonado Galdeano C, de Moreno de LeBlanc A, Perdigon G (2015) Lactobacillus casei CRL 431 administration decreases inflammatory cytokines in a diet-induced obese mouse model. Nutrition 31(7–8):1000–1007. https://doi.org/10.1016/j.nut.2015.02.006 CrossRefPubMed

40.

Yoshida H, Miura S, Kishikawa H, Hirokawa M, Nakamizo H, Nakatsumi RC, Suzuki H, Saito H, Ishii H (2001) Fatty acids enhance GRO/CINC-1 and interleukin-6 production in rat intestinal epithelial cells. J Nutr 131(11):2943–2950CrossRef

41.

Miura S, Tsuzuki Y, Hokari R, Ishii H (1998) Modulation of intestinal immune system by dietary fat intake: relevance to Crohn’s disease. J Gastroenterol Hepatol 13(12):1183–1190CrossRef

42.

Arngrim N, Simonsen L, Holst JJ, Bulow J (2013) Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects: a possible link between obesity and local tissue inflammation? Int J Obes (Lond) 37(5):748–750. https://doi.org/10.1038/ijo.2012.98 CrossRef

43.

Huang FP, Platt N, Wykes M, Major JR, Powell TJ, Jenkins CD, MacPherson GG (2000) A discrete subpopulation of dendritic cells transports apoptotic intestinal epithelial cells to T cell areas of mesenteric lymph nodes. J Exp Med 191(3):435–444CrossRef

44.

Worthington JJ, Czajkowska BI, Melton AC, Travis MA (2011) Intestinal dendritic cells specialize to activate transforming growth factor-beta and induce Foxp3+ regulatory T cells via integrin alphavbeta8. Gastroenterology 141(5):1802–1812. https://doi.org/10.1053/j.gastro.2011.06.057 CrossRefPubMedPubMedCentral

45.

Sun JB, Czerkinsky C, Holmgren J (2007) Sublingual ‘oral tolerance’ induction with antigen conjugated to cholera toxin B subunit generates regulatory T cells that induce apoptosis and depletion of effector T cells. Scand J Immunol 66(2–3):278–286. https://doi.org/10.1111/j.1365-3083.2007.01975.x CrossRefPubMed

46.

Hadis U, Wahl B, Schulz O, Hardtke-Wolenski M, Schippers A, Wagner N, Muller W, Sparwasser T, Forster R, Pabst O (2011) Intestinal tolerance requires gut homing and expansion of FoxP3+ regulatory T cells in the lamina propria. Immunity 34(2):237–246. https://doi.org/10.1016/j.immuni.2011.01.016 CrossRefPubMed

47.

Worbs T, Bode U, Yan S, Hoffmann MW, Hintzen G, Bernhardt G, Forster R, Pabst O (2006) Oral tolerance originates in the intestinal immune system and relies on antigen carriage by dendritic cells. J Exp Med 203(3):519–527. https://doi.org/10.1084/jem.20052016 CrossRefPubMedPubMedCentral

48.

Schulz O, Jaensson E, Persson EK, Liu X, Worbs T, Agace WW, Pabst O (2009) Intestinal CD103+, but not CX3CR51+, antigen sampling cells migrate in lymph and serve classical dendritic cell functions. J Exp Med 206(13):3101–3114. https://doi.org/10.1084/jem.20091925 CrossRefPubMedPubMedCentral

Titel: High-fat diet induced central adiposity (visceral fat) is associated with increased fibrosis and decreased immune cellularity of the mesenteric lymph node in mice
verfasst von: Aaron M. Magnuson
Daniel P. Regan
Andrea D. Booth
Josephine K. Fouts
Claudia M. Solt
Jessica L. Hill
Steve W. Dow
Michelle T. Foster
Publikationsdatum: 04.06.2019
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nutrition / Ausgabe 4/2020
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-019-02019-z

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High-fat diet induced central adiposity (visceral fat) is associated with increased fibrosis and decreased immune cellularity of the mesenteric lymph node in mice