Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease

Crohn's disease (CD) is characterized by inflammation and an aetiology that is still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity, as this fat covers the entire length of the affected area. Adipocytes synthesize leptin and adiponectin, adipocytokines responsible for pro‐ and anti‐inflammatory effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well as mesenteral expression of adiponectin in active CD and those in remission. Sixteen patients with ileocaecal CD followed at the Outpatient Clinic, Coloproctology Unit of University of Campinas Clinical Hospital, participated in the study. Analysis of serum adiponectin and leptin by enzyme‐linked immunosorbent assay was performed in patients with active CD (ACD group), remission CD (RCD group) and in six healthy controls. Ten patients with active ileocaecal CD (FCD group) and eight patients with non‐inflammatory disease selected for surgery were also studied. The specimens were snap‐frozen and the expression of adiponectin was determined by immunoblot of protein extracts. Serum C‐reactive protein levels were higher in the ACD group when compared to the others and no difference of body mass index was observed between the groups. Serum adiponectin was lower in the ACD group when compared to control, but no differences were seen when comparing the ACD and RCD groups. Mesenteric adiponectin expression was lower in the FCD group when compared to the FC group. Serum leptin was similar in all groups. The lower levels of serum and mesenteric adiponectin in active CD suggest a defective regulation of anti‐inflammatory pathways in CD pathogenesis.

[1]  L. Gilardini,et al.  Visceral adipocytes: old actors in obesity and new protagonists in Crohn's disease? , 2011, Gut.

[2]  C. Hawkey,et al.  Ratio of visceral to subcutaneous fat area is a biomarker of complicated Crohn's disease. , 2011, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[3]  R. Arsenescu,et al.  Adiponectin and Plant-Derived Mammalian Adiponectin Homolog Exert a Protective Effect in Murine Colitis , 2011, Digestive Diseases and Sciences.

[4]  H. Guillou,et al.  Is Crohn's creeping fat an adipose tissue? , 2011, Inflammatory Bowel Diseases.

[5]  T. Ziegler,et al.  Diverse roles of leptin in the gastrointestinal tract: modulation of motility, absorption, growth, and inflammation. , 2011, Nutrition.

[6]  B. Siegmund,et al.  Extraluminal factors contributing to inflammatory bowel disease. , 2011, World journal of gastroenterology.

[7]  F. Liu,et al.  DsbA-L Alleviates Endoplasmic Reticulum Stress–Induced Adiponectin Downregulation , 2010, Diabetes.

[8]  G. Rogler,et al.  Circulating levels of chemerin and adiponectin are higher in ulcerative colitis and chemerin is elevated in Crohn's disease , 2010, Inflammatory bowel diseases.

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

[10]  J. Schölmerich,et al.  The role of adiponectin in inflammatory gastrointestinal diseases , 2009, Gut.

[11]  U. Schweizer,et al.  Circulating adipokines and the protective effects of hyperinsulinemia in inflammatory bowel disease. , 2009, Nutrition.

[12]  E. Kouroumalis,et al.  Leptin, adiponectin, resistin, and ghrelin--implications for inflammatory bowel disease. , 2008, Molecular nutrition & food research.

[13]  Judy H. Cho,et al.  The genetics and immunopathogenesis of inflammatory bowel disease , 2008, Nature Reviews Immunology.

[14]  G. Fantuzzi Adiponectin and inflammation: consensus and controversy. , 2008, The Journal of allergy and clinical immunology.

[15]  J. Arthur,et al.  Insulin, leptin, and adiponectin receptors in colon: regulation relative to differing body adiposity independent of diet and in response to dimethylhydrazine. , 2007, American journal of physiology. Gastrointestinal and liver physiology.

[16]  G. Fantuzzi,et al.  Adiponectin deficiency protects mice from chemically induced colonic inflammation. , 2007, Gastroenterology.

[17]  M. Chamaillard,et al.  Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander? , 2006, Gut.

[18]  M. Zeitz,et al.  Toll‐Like Receptor Expression and Response to Specific Stimulation in Adipocytes and Preadipocytes , 2006, Annals of the New York Academy of Sciences.

[19]  C. Pond,et al.  Perinodal Adipose Tissue and Fatty Acid Composition of Lymphoid Tissues in Patients with and without Crohn's Disease and Their Implications for the Etiology and Treatment of CD , 2006, Annals of the New York Academy of Sciences.

[20]  G. Rogler,et al.  Profiling adipocytokine secretion from creeping fat in Crohn's disease , 2006, Inflammatory bowel diseases.

[21]  H. Cai,et al.  Induction of leptin resistance through direct interaction of C-reactive protein with leptin , 2006, Nature Medicine.

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

[23]  L. Pizzi,et al.  Impact of chronic conditions on quality of life in patients with inflammatory bowel disease , 2006, Inflammatory bowel diseases.

[24]  C. Wen,et al.  Plasma leptin and ghrelin concentrations in patients with Crohn's disease. , 2005, World journal of gastroenterology.

[25]  R. Vettor,et al.  Review article: adipocytokines and insulin resistance , 2005, Alimentary pharmacology & therapeutics.

[26]  E. Kouroumalis,et al.  The Emerging Role of Adipocytokines as Inflammatory Mediators in Inflammatory Bowel Disease , 2005, Inflammatory bowel diseases.

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

[28]  S. Kihara,et al.  Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn’s disease , 2005, Gut.

[29]  G. Fantuzzi Adipose tissue, adipokines, and inflammation. , 2005, The Journal of allergy and clinical immunology.

[30]  L. Velloso,et al.  Short-term in vivo inhibition of insulin receptor substrate-1 expression leads to insulin resistance, hyperinsulinemia, and increased adiposity. , 2005, Endocrinology.

[31]  J. Schölmerich,et al.  Mechanisms of Disease: adipocytokines and visceral adipose tissue—emerging role in intestinal and mesenteric diseases , 2005, Nature Clinical Practice Gastroenterology &Hepatology.

[32]  F. Casanueva,et al.  Leptin, from fat to inflammation: old questions and new insights , 2005, FEBS letters.

[33]  R. Busse,et al.  From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. , 2004, Diabetes.

[34]  T. Ziegler,et al.  Colonic leptin: source of a novel pro‐inflammatory cytokine involved in inflammatory bowel disease , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

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

[36]  S. Kihara,et al.  Obesity, adiponectin and vascular inflammatory disease , 2003, Current opinion in lipidology.

[37]  J. Galmiche,et al.  Overexpression of leptin mRNA in mesenteric adipose tissue in inflammatory bowel diseases. , 2003, Gastroenterologie clinique et biologique.

[38]  R. Henry,et al.  Adiponectin: more than just another fat cell hormone? , 2003, Diabetes care.

[39]  M. Lisanti,et al.  The Lipopolysaccharide-activated Toll-like Receptor (TLR)-4 Induces Synthesis of the Closely Related Receptor TLR-2 in Adipocytes* , 2000, The Journal of Biological Chemistry.

[40]  I. Sobhani,et al.  Leptin secretion and leptin receptor in the human stomach , 2000, Gut.

[41]  C. Kahn,et al.  Cross-talk between the insulin and angiotensin signaling systems. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

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

[43]  M. M. Bradford A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[44]  F Kern,et al.  Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study. , 1976, Gastroenterology.