Role of fat and adipokines in intestinal inflammation

Current Opinion in Gastroenterology

Volumn 30, Issue 6, 2014, Pages 561-565

  Kredel, Leai ^a   Batra, Arvind ^a   Siegmund, Britta ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Adipokines; Adipose tissue; Creeping fat; Crohn's disease; Intestinal inflammation

Indexed keywords

ADIPOCYTOKINE; ADIPONECTIN; FAT; LEPTIN; RESISTIN; ADIPONECTIN RECEPTOR; AUTACOID; BIOLOGICAL MARKER; CELL SURFACE RECEPTOR; LEPTIN RECEPTOR;

ADAPTIVE IMMUNITY; ADIPOCYTE; ADIPOSE TISSUE; BACTERIAL TRANSLOCATION; CELL INFILTRATION; CROHN DISEASE; ENTERITIS; HUMAN; IMMUNOCOMPETENT CELL; LIPOHYPERTROPHY; PHENOTYPE; PROTEIN FUNCTION; REVIEW; IMMUNOLOGY; INFLAMMATION; INFLAMMATORY BOWEL DISEASE; INTESTINE MUCOSA; LIPID METABOLISM; MESENTERY; METABOLISM; SECRETION (PROCESS);

ADIPOKINES; ADIPOSE TISSUE; BIOLOGICAL MARKERS; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; INFLAMMATORY BOWEL DISEASES; INTESTINAL MUCOSA; LEPTIN; LIPID METABOLISM; MESENTERY; RECEPTORS, ADIPONECTIN; RECEPTORS, CELL SURFACE; RECEPTORS, LEPTIN; RESISTIN;

EID: 84927588792     PISSN: 02671379     EISSN: 15317056     Source Type: Journal    
DOI: 10.1097/MOG.0000000000000116     Document Type: Review

References (88)

1. Hoffmann JC, Preiß JC, Autschbach F, et al. S3-Leitlinie 'Diagnostik und Therapie des Morbus Crohn' Ergebnisse einer Evidenz-basierten Konsensuskonferenz der Deutschen Gesellschaft für Verdauungs- und Stoffwechselkrankheiten zusammen mit dem Kompetenznetz Chronisch entzündliche Darmerkrankungen [Clinical practice guideline on diagnosis and treatment of Crohn's disease]. Z Gastroenterol 2008;46:1094-1146.
2. Crohn BB. Regional ileitis, a pathologic an clinical entity. J Am Med Assac 1932;99:1323-1329.
3. Fink C, Karagiannides I, Bakirtzi K, Pothoulakis C. Adipose tissue and inflammatory bowel disease pathogenesis. Inflamm Bowel Dis 2012;18:1550-1557. Excellent review regarding the potential role of fat in Crohn's disease pathogenesis.
4. Peyrin-Biroulet L, Chamaillard M, Gonzalez F, et al. Mesenteric fat in Crohn's disease: apathogeneti chall mark oraninnocent by stander? Gut 2007;56:577-583.
5. Sheehan AL, Warren BF, Gear MW, Shepherd NA. Fat-wrapping in Crohn's disease: pathological basis and relevance to surgical practice. Br J Surg 1992;79:955-958.
6. Fruhbeck G. Overview of adipose tissue and its role in obesity and metabolic disorders. Methods Mol Biol 2008;456:1-22.
7. Carvalheira JB, Qiu Y, Chawla A. Blood spotlight on leukocytes and obesity. Blood 2013;122:3263-3267.
8. Han JM, Levings MK. Immune regulation in obesity-associated adipose inflammation. J Immunol 2013;191:527-532.
9. Kopp A, Buechler C, Bala M, et al. Toll-like receptor ligands cause proinflammatory and prodiabetic activation of adipocytes via phosphorylation of extracellular signal-regulated kinase and c-Jun. N-terminal kinase but not interferon regulatory factor-3. Endocrinology 2010;151:1097-1108.
10. Schaffler A, Scholmerich J, Salzberger B. Adipose tissue as an immunological organ: toll-like receptors, C1q/TNFs and CTRPs. Trends Immunol 2007;28:393-399.
11. Drouet M, Dubuquoy L, Desreumaux P, Bertin B. Visceral fat and gut inflammation. Nutrition 2012;28:113-117.
12. Batra A, Pietsch J, Fedke I, et al. Leptin-dependent toll-like receptor expression and responsiveness in preadipocytes and adipocytes. Am J Pathol 2007;170:1931-1941.
13. Faggioni R, Jones-Carson J, Reed DA, et al. Leptin-deficient (ob/ob) mice are protected from T cell-mediated hepatotoxicity: role of tumor necrosis factor alpha and IL-18. Proc Natl Acad Sci U S A 2000;97:2367-2372.
14. Fantuzzi G, Faggioni R. Leptin in the regulation of immunity, inflammation, and hematopoiesis. J Leukoc Biol 2000;68:437-446.
15. Siegmund B, Lear-Kaul KC, Faggioni R, Fantuzzi G. Leptin deficiency, not obesity, protects mice from Con A-induced hepatitis. Eur J Immunol 2002;32:552-560.
16. Fayad R, Pini M, Sennello JA, et al. Adiponectin deficiency protects mice from chemically induced colonic inflammation. Gastroenterology 2007;132:601-614.
17. Garaulet M, Hernandez-Morante JJ, de Heredia FP, Tebar FJ. Adiponectin, the controversial hormone. Public Health Nutr 2007;10:1145-1150.
18. Charriere G, Cousin B, Arnaud E, et al. Preadipocyte conversion to macrophage. Evidence of plasticity. J Biol Chem 2003;278:9850-9855.
19. Cousin B, Munoz O, Andre M, et al. A role for preadipocytes as macrophagelike cells. FASEB J 1999;13:305-312.
20. Ritchie SA, Connell JM. The link between abdominalobesity, metabolicsyndrome and cardiovascular disease. Nutr Metab Cardiovasc Dis 2007;17:319-326.
21. Hass DJ, Brensinger CM, Lewis JD, Lichtenstein GR. The impact of increased body mass index on the clinical course of Crohn's disease. Clin Gastroenterol Hepatol 2006;4:482-488.
22. Blain A, Cattan S, Beaugerie L, et al. Crohn's disease clinical course and severity in obese patients. Clin Nutr 2002;21:51-57.
23. Harper JW, Sinanan MN, Zisman TL. Increased body mass index is associated with earlier time to loss of response to infliximab in patients with inflammatory bowel disease. Inflamm Bowel Dis 2013;19:2118-2124. This study underlines the therapeutic consequences gastroenterologists are confronted with in view of the worldwide increase in obesity.
24. Schaffler A, Scholmerich J, Buchler C. Mechanisms of disease: adipocytokines and visceral adipose tissue-emerging role in intestinal and mesenteric diseases. Nat Clin Pract Gastroenterol Hepatol 2005;2:103-111.
25. Pauls S, Kratzer W, Rieber A, et al. [Quantifying the inflammatory activity in Crohn's disease using CE dynamic MRI]. Rofo 2003;175:1093-1099.
26. Zulian A, Cancello R, Ruocco C, et al. Differences in visceral fat and fat bacterial colonization between ulcerative colitis and Crohn's disease. An in vivo and in vitro study. PLoS One 2013;8:e78495. The authors highlight the difference between Crohn's disease and ulcerative colitis in terms of mesenteric fat morphology and bacterial translocation. Here, bacterial translocation is enhanced in Crohn's disease and is followed by adipocyte proliferation.
27. Yamamoto K, Kiyohara T, Murayama Y, et al. Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease. Gut 2005;54:789-796.
28. Kredel LI, Batra A, Stroh T, et al. Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn's disease. Gut 2012;6:852-862. In this study, we were able to define regulatory macrophages as a dominant cell population within the mesenteric fat of Crohn's disease.
29. Paul G, Schaffler A, Neumeier M, et al. Profiling adipocytokine secretion from creeping fat in Crohn's disease. Inflamm Bowel Dis 2006;12:471-477.
30. Barbier M, Vidal H, Desreumaux P, et al. Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. Gastroenterol Clin Biol 2003;27:987-991.
31. Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000;62:413-437.
32. Madej T, Boguski MS, Bryant SH. Threading analysis suggests that the obese gene product may be a helical cytokine. FEBS Lett 1995;373:13-18.
33. Lord GM, Matarese G, Howard JK, et al. Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 1998;394:897-901
34. Lord GM, Matarese G, Howard JK, et al. Leptin inhibits the anti-CD3-driven proliferation of peripheral blood T cells but enhances the production of proinflammatory cytokines. J Leukoc Biol 2002;72:330-338.
35. Scheibenbogen C, Keilholz U, Richter M, et al. The interleukin-2 receptor in human monocytes and macrophages: regulation of expression and release of the alpha and beta chains (p55 and p75). Res Immunol 1992;143:33-37.
36. Darcissac EC, Bahr GM, Parant MA, et al. Selective induction of CD11a, b, c/CD18 and CD54 expression at the cell surface of human leukocytes by muramyl peptides. Cell Immunol 1996;169:294-301.
37. Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol 1999;194:6-11.
38. Martin-Romero C, Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human leptin enhances activation and proliferation of human circulating T lymphocytes. Cell Immunol 2000;199:15-24.
39. Dixit VD, Mielenz M, Taub DD, Parvizi N. Leptin induces growth hormone secretion from peripheral blood mononuclear cells via a protein kinase C- and nitric oxide-dependent mechanism. Endocrinology 2003;144:5595-5603.
40. Gainsford T, Willson TA, Metcalf D, et al. Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells. Proc Natl Acad Sci U S A 1996;93:14564-14568.
41. Siegmund B, Lehr HA, Fantuzzi G. Leptin: a pivotal mediator of intestinal inflammation in mice. Gastroenterology 2002;122:2011-2025.
42. Siegmund B, Sennello JA, Jones-Carson J, et al. Leptin receptor expression on T lymphocytes modulates chronic intestinal inflammation in mice. Gut 2004;53:965-972.
43. Sitaraman S, Liu X, Charrier L, et al. Colonic leptin: source of a novel proinflammatory cytokine involved in IBD. FASEB J 2004;18:696-698.
44. Le Drean G, Haure-Mirande V, Ferrier L, et al. Visceral adipose tissue and leptin increase colonic epithelial tight junction permeability via a RhoA-ROCKdependent pathway. FASEB J 2013;28:1059-1070. The authors reveal a mechanism by which visceral fat and adipocyte-derived leptin might lead to mucosal barrier defect under circumstances of adipose tissue accumulation.
45. Duggal P, Guo X, Haque R, et al. A mutation in the leptin receptor is associated with Entamoeba histolytica infection in children. J Clin Invest 2012;121:1191-1198.
46. Madan R, Guo X, Naylor C, et al. Role of leptin-mediated colonic inflammation in defense against Clostridium difficile colitis. Infect Immun 2013;82:341-349.
47. Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab 1999;84:3686-3695.
48. Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002;110:1093-1103.
49. Okamoto Y, Folco EJ, Minami M, et al. Adiponectin inhibits the production of CXC receptor 3 chemokine ligands in macrophages and reduces T-lymphocyte recruitment in atherogenesis. Circ Res 2008;102:218-225.
50. Folco EJ, Rocha VZ, Lopez-Ilasaca M, Libby P. Adiponectin inhibits proinflammatory signaling in human macrophages independent of interleukin-10. J Biol Chem 2009;284:25569-25575.
51. Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116:1784-1792.
52. Lovren F, Pan Y, Quan A, et al. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol 2010;299:H656-H663.
53. Desreumaux P, Ernst O, Geboes K, et al. Inflammatory alterations in mesenteric adipose tissue in Crohn's disease. Gastroenterology 1999;117:73-81.
54. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005;26:439-451.
55. Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T. Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab 2013;28:15-23.
56. Tsatsanis C, Zacharioudaki V, Androulidaki A, et al. Adiponectin induces TNFalpha and IL-6 in macrophages and promotes tolerance to itself and other proinflammatory stimuli. Biochem Biophys Res Commun 2005;335:1254-1263.
57. Kumada M, Kihara S, Ouchi N, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004;109:2046-2049.
58. Zacharioudaki V, Androulidaki A, Arranz A, et al. Adiponectin promotes endotoxin tolerance in macrophages by inducing IRAK-M expression. J Immunol 2009;182:6444-6451.
59. Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a newmember of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 2000;96:1723-1732.
60. Yamaguchi N, Argueta JG, Masuhiro Y, et al. Adiponectin inhibits toll-like receptor family-induced signaling. FEBS Lett 2005;579:6821-6826.
61. Wulster-Radcliffe MC, Ajuwon KM, Wang J, et al. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun 2004;316:924-929.
62. Nishihara T, Matsuda M, Araki H, et al. Effect of adiponectin on murine colitis induced by dextran sulfate sodium. Gastroenterology 2006;131:853-861.
63. Saxena A, Fletcher E, Larsen B, et al. Effect of exercise on chemically-induced colitis in adiponectin deficient mice. J Inflamm (Lond) 2012;9:30.
64. Ouchi N, Kihara S, Funahashi T, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003;107:671-674.
65. Valentini L, Wirth EK, Schweizer U, et al. Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease. Nutrition 2009;25:172-181.
66. Karmiris K, Koutroubakis IE, Xidakis C, et al. Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease. Inflamm Bowel Dis 2006;12:100-105.
67. Rodrigues VS, Milanski M, Fagundes JJ, et al. Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease. Clin Exp Immunol 2012;170:358-364. This study contributes to the understanding of adipokines in Crohn's disease by underlining differences between local and systemic mediator concentrations.
68. Karmiris K, Koutroubakis IE. Resistin: another rising biomarker in inflammatory bowel disease? Eur J Gastroenterol Hepatol 2007;19:1035-1037.
69. Park HK, Ahima RS. Resistin in rodents and humans. Diabetes Metab J 2014;37:404-414. The authors provide a concise summary about this understudied adipokine in mice and men.
70. Bokarewa M, Nagaev I, Dahlberg L, et al. Resistin, an adipokine with potent proinflammatory properties. J Immunol 2005;174:5789-5795.
71. Silswal N, Singh AK, Aruna B, et al. Human resistin stimulates the proinflammatory cytokines TNF-alpha and IL-12 in macrophages by NF-kappaBdependent pathway. Biochem Biophys Res Commun 2005;334:1092-1101.
72. Konrad A, Lehrke M, Schachinger V, et al. Resistin is an inflammatory marker of inflammatory bowel disease in humans. Eur J Gastroenterol Hepatol 2007;19:1070-1074.
73. Clemente TR, Dos Santos AN, Sturaro JN, et al. Infliximab modifies mesenteric adipose tissue alterations and intestinal inflammation in rats with TNBSinduced colitis. Scand J Gastroenterol 2012;47:943-950. Provides interesting data how anti-TNF-therapy might modify.
74. Peyrin-Biroulet L, Gonzalez F, Dubuquoy L, et al. Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease. Gut 2012;61:78-85. This article could prove the mesenteric fat tissue to be a second important source for CRP in Crohn's disease, revealing one possible mechanism how creeping fat might contribute to intestinal and systemic inflammation.
75. Stroh T, Batra A, Glauben R, et al. Nucleotide oligomerization domains 1 and 2: regulation of expression and function in preadipocytes. J Immunol 2008;181:3620-3627.
76. Batra A, Heimesaat MM, Bereswill S, et al. Mesenteric fat - control site for bacterial translocation in colitis? Mucosal Immunol 2012;5:580-591. Our group could show bacterial translocation in intestinal inflammation and specify the effector response of the adjacent mesenteric fat.
77. Pond CM. Adipose tissue and the immune system. Prostaglandins Leukot Essent Fatty Acids 2005;73:17-30.
78. Behr MA. The path to Crohn's disease: is mucosal pathology a secondary event? Inflamm Bowel Dis 2010;16:896-902.
79. Bertin B, Desreumaux P, Dubuquoy L. Obesity visceral fat and Crohn's disease. Curr Opin Clin Nutr Metab Care 2010;13:574-580.
80. Neyrolles O, Hernandez-Pando R, Pietri-Rouxel F, et al. Is adipose tissue a place for Mycobacterium tuberculosis persistence? PLoS One 2006;1:e43.
81. Bechah Y, Paddock CD, Capo C, et al. Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model. PLoS One 2010;5:e8547.
82. Drouet M, Dubuquoy L, Desreumaux P, Bertin B. Visceral fat and gut inflammation. Nutrition 2012;28:113-117.
83. Fink C, Karagiannides I, Bakirtzi K, Pothoulakis C. Adipose tissue and inflammatory bowel disease pathogenesis. Inflamm Bowel Dis 2012;8:1550-1557.
84. Okuno A, Tamemoto H, Tobe K, et al. Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 1998;101:1354-1361.
85. Zulian A, Cancello R, Micheletto G, et al. Visceral adipocytes: old actors in obesity and new protagonists in Crohn's disease? Gut 2012;61:86-94. This study summarizes in detail the specific features of creeping fat.
86. Skurk T, Alberti-Huber C, Herder C, Hauner H. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007;92:1023-1033.
87. Weber M, Sporrer D, Weigert J, et al. Adiponectin downregulates galectin-3 whose cellular form is elevated whereas its soluble form is reduced in type 2 diabetic monocytes. FEBS Lett 2009;583:3718-3724.
88. Jung SH, Saxena A, Kaur K, et al. The role of adipose tissue-associated macrophages and T lymphocytes in the pathogenesis of inflammatory bowel disease. Cytokine 2013;61:459-468. The authors focus on the important functions of immune cells within the mesenteric tissue and their impact on intestinal inflammation.