The Mesenteric Fat and Intestinal Muscle Interface: Creeping Fat Influencing Stricture Formation in Crohn's Disease.

Adipose tissue is present in close proximity to various organs in the human body. One prominent example is fat contained in the mesentery that is contiguous with all abdominal digestive organs including the intestine. Despite the fact that mesenteric fat-wrapping around the inflamed gut (so called "creeping fat") was described as a characteristic feature of Crohn's disease (CD) in the early 1930s, the functional implications of creeping fat have received only recent attention. As a potent producer of fatty acids, cytokines, growth factors, and adipokines, creeping fat plays an important role in regulation of immunity and inflammation. Increasing evidence points to a link between creeping fat and intestinal inflammation in CD, where histopathologic evaluation shows a significant association between creeping fat and connective tissue changes in the bowel wall, such as muscular hypertrophy, fibrosis, and stricture formation. In addition, emerging mechanistic data indicate a link between creeping fat, muscularis propria hyperplasia, and stricturing disease. Information on fat-mesenchymal interactions in other organs could provide clues to fill the fundamental knowledge gap on the role of distinct components of creeping fat in intestinal fibrosis and stricture formation. Future studies will provide important new information that in turn could lead to novel therapeutic agents aimed at prevention or treatment of CD-associated fibrosis and stricture formation.

[1]  C. Fiocchi,et al.  629 - Creeping-Fat Derived Free Fatty Acids Induce Hyperplasia of Intestinal Muscularis Propria Muscle Cells – A Novel Link Between Fat and Intestinal Stricture Formation in Crohn's Disease , 2018 .

[2]  P. Gao,et al.  Adenovirus-mediated knockdown of activin A receptor type 2A attenuates immune-induced hepatic fibrosis in mice and inhibits interleukin-17-induced activation of primary hepatic stellate cells , 2018, International journal of molecular medicine.

[3]  K. Clément,et al.  Visceral Adipose Tissue Drives Cardiac Aging Through Modulation of Fibroblast Senescence by Osteopontin Production , 2018, Circulation.

[4]  W. Sandborn,et al.  Consensus Recommendations for Evaluation, Interpretation, and Utilization of Computed Tomography and Magnetic Resonance Enterography in Patients With Small Bowel Crohn's Disease. , 2018, Gastroenterology.

[5]  F. Shanahan,et al.  Inclusion of the Mesentery in Ileocolic Resection for Crohn’s Disease is Associated With Reduced Surgical Recurrence , 2018, Journal of Crohn's & colitis.

[6]  P. Rensen,et al.  Targeting white, brown and perivascular adipose tissue in atherosclerosis development , 2017, European journal of pharmacology.

[7]  B. Hinz,et al.  Activin A in Inflammation, Tissue Repair, and Fibrosis: Possible Role as Inflammatory and Fibrotic Mediator of Uterine Fibroid Development and Growth , 2017, Seminars in Reproductive Medicine.

[8]  T. Griffin,et al.  Profibrotic Infrapatellar Fat Pad Remodeling Without M1 Macrophage Polarization Precedes Knee Osteoarthritis in Mice With Diet‐Induced Obesity , 2017, Arthritis & rheumatology.

[9]  S. Konstantinides,et al.  Perivascular adipose tissue: epiphenomenon or local risk factor? , 2017, International Journal of Obesity.

[10]  J. C. Coffey,et al.  Defining the mesentery as an organ and what this means for understanding its roles in digestive disorders , 2017, Expert review of gastroenterology & hepatology.

[11]  J. Coffey,et al.  Histology of the mesentery , 2017 .

[12]  R. Sehgal,et al.  Embryologic development of the mesentery, peritoneal reflection, and Toldt's fascia , 2017 .

[13]  K. Clément,et al.  Knee and hip intra-articular adipose tissues (IAATs) compared with autologous subcutaneous adipose tissue: a specific phenotype for a central player in osteoarthritis , 2017, Annals of the rheumatic diseases.

[14]  J. C. Coffey,et al.  The mesentery: structure, function, and role in disease. , 2016, The lancet. Gastroenterology & hepatology.

[15]  D. O'Leary,et al.  The mesentery in Crohn's disease: friend or foe? , 2016, Current opinion in gastroenterology.

[16]  S. Hatem,et al.  Cardiac adipose tissue and atrial fibrillation: the perils of adiposity. , 2016, Cardiovascular research.

[17]  K. Clément,et al.  Human epicardial adipose tissue has a specific transcriptomic signature depending on its anatomical peri-atrial, peri-ventricular, or peri-coronary location. , 2015, Cardiovascular research.

[18]  J. Filosa,et al.  Adipocyte-Derived Hormone Leptin Is a Direct Regulator of Aldosterone Secretion, Which Promotes Endothelial Dysfunction and Cardiac Fibrosis , 2015, Circulation.

[19]  K. Clément,et al.  Human epicardial adipose tissue induces fibrosis of the atrial myocardium through the secretion of adipo-fibrokines. , 2015, European heart journal.

[20]  F. Magro,et al.  Metabolic Inflammation in Inflammatory Bowel Disease: Crosstalk Between Adipose Tissue and Bowel , 2015, Inflammatory bowel diseases.

[21]  B. Siegmund,et al.  Adipose-Tissue and Intestinal Inflammation – Visceral Obesity and Creeping Fat , 2014, Front. Immunol..

[22]  C. Fiocchi,et al.  573 Adipocyte and Preadipocyte Derived-Mediators Induce a PRO-Fibrogenic Phenotype in Human Intestinal Mesenchymal Cells -A Novel Link Between Fat and Intestinal Fibrosis , 2014 .

[23]  Bruce M. Spiegelman,et al.  What We Talk About When We Talk About Fat , 2014, Cell.

[24]  S. Sacre,et al.  Emerging Role of Endosomal Toll-Like Receptors in Rheumatoid Arthritis , 2013, Front. Immunol..

[25]  J. Coffey,et al.  Circulating fibrocytes and Crohn's disease , 2013, The British journal of surgery.

[26]  S. Friedman,et al.  Therapy for Fibrotic Diseases: Nearing the Starting Line , 2013, Science Translational Medicine.

[27]  T. Kanneganti,et al.  Immunological complications of obesity , 2012, Nature Immunology.

[28]  M. Zeitz,et al.  Adipokines from local fat cells shape the macrophage compartment of the creeping fat in Crohn's disease , 2012, Gut.

[29]  C. Hofmann,et al.  C1q/TNF‐related protein‐3 (CTRP‐3) is secreted by visceral adipose tissue and exerts antiinflammatory and antifibrotic effects in primary human colonic fibroblasts , 2011, Inflammatory bowel diseases.

[30]  L. Peyrin-Biroulet,et al.  Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease , 2011, Gut.

[31]  A. Gambero,et al.  Perinodal Adipose Tissue and Mesenteric Lymph Node Activation During Reactivated TNBS-Colitis in Rats , 2011, Digestive Diseases and Sciences.

[32]  A. Zinsmeister,et al.  Risk factors associated with progression to intestinal complications of Crohn's disease in a population-based cohort. , 2010, Gastroenterology.

[33]  Udo Hoffmann,et al.  Pericardial Fat Is Associated With Prevalent Atrial Fibrillation: The Framingham Heart Study , 2010, Circulation. Arrhythmia and electrophysiology.

[34]  J. Hughes,et al.  Macrophages and renal fibrosis. , 2010, Seminars in nephrology.

[35]  M. Zeitz,et al.  Adipokine signaling in inflammatory bowel disease. , 2009, Inflammatory bowel diseases.

[36]  P. Rajiah,et al.  Utility of high-resolution MR imaging in demonstrating transmural pathologic changes in Crohn disease. , 2009, Radiographics : a review publication of the Radiological Society of North America, Inc.

[37]  G. Rogler,et al.  Secretion of RANTES (CCL5) and interleukin‐10 from mesenteric adipose tissue and from creeping fat in Crohn’s disease: Regulation by steroid treatment , 2006, Journal of gastroenterology and hepatology.

[38]  Sabine Werner,et al.  Roles of activin in tissue repair, fibrosis, and inflammatory disease. , 2006, Cytokine & growth factor reviews.

[39]  E. Kouroumalis,et al.  Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease , 2006, Inflammatory bowel diseases.

[40]  J. Montani,et al.  Mature adipocytes and perivascular adipose tissue stimulate vascular smooth muscle cell proliferation: effects of aging and obesity. , 2005, American journal of physiology. Heart and circulatory physiology.

[41]  P. Sharma,et al.  Gastro-oesophageal reflux disease: symptoms, erosions, and Barrett’s—what is the interplay? , 2005, Gut.

[42]  L. Beaugerie,et al.  Impact of the increasing use of immunosuppressants in Crohn’s disease on the need for intestinal surgery , 2005, Gut.

[43]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[44]  D. Jewell,et al.  The relationship between inflammatory and serosal connective tissue changes in ileal Crohn's disease: evidence for a possible causative link , 2000, The Journal of pathology.

[45]  J. Auwerx,et al.  Inflammatory alterations in mesenteric adipose tissue in Crohn's disease. , 1999, Gastroenterology.

[46]  J. Levine,et al.  Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth. , 1998, The Journal of clinical investigation.

[47]  N. Shepherd,et al.  Fat‐wrapping in Crohn's disease: Pathological basis and relevance to surgical practice , 1992, The British journal of surgery.

[48]  M. Spach,et al.  Relating Extracellular Potentials and Their Derivatives to Anisotropic Propagation at a Microscopic Level in Human Cardiac Muscle: Evidence for Electrical Uncoupling of Side‐to‐Side Fiber Connections with Increasing Age , 1986, Circulation research.

[49]  G. Oppenheimer,et al.  Landmark article Oct 15, 1932. Regional ileitis. A pathological and clinical entity. By Burril B. Crohn, Leon Ginzburg, and Gordon D. Oppenheimer. , 1984, JAMA.

[50]  G. Rogler,et al.  Mechanisms, Management, and Treatment of Fibrosis in Patients With Inflammatory Bowel Diseases. , 2017, Gastroenterology.

[51]  REGIONAL ILEITISA PATHOLOGIC AND CLINICAL ENTITY , 2008 .