title: Leptin: a pivotal mediator of intestinal inflammation in mice.
abstract: OBJECTIVE
  In addition to acting as a regulator of food intake and energy expenditure, leptin can also modulate immune and inflammatory responses. The role of leptin in intestinal inflammation is the focus of the present study.
  
  
  METHODS
  Acute and chronic colitis were induced in leptin-deficient ob/ob or wild-type (WT) mice using dextran sulfate sodium (DSS) or trinitrobenzene sulfonic acid (TNBS). The severity of colitis was evaluated, and possible mechanisms were studied.
  
  
  RESULTS
  Leptin directly stimulates intraepithelial lymphocytes (IELs) and lamina propria mononuclear cells (LPMCs). In the DSS acute model, ob/ob mice exhibited a 72% reduction of colitis severity and spontaneous release of proinflammatory cytokines from the colon compared with WT mice. Replacement of leptin in ob/ob mice converted disease resistance to susceptibility, indicating that leptin deficiency, not obesity, accounts for the resistance to acute DSS-induced colitis. During chronic DSS-induced colitis and TNBS-induced colitis, in addition to reduced disease severity, ob/ob mice exhibited a significant attenuation in intestinal inflammation, accompanied by reduced production of cytokines and chemokines. When compared with WT mice, CD8(+) IELs of ob/ob mice were reduced in number as well as in their ability to synthesize interferon gamma. In addition, LPMCs of ob/ob mice showed increased apoptosis in untreated as well as DSS- or TNBS-treated mice. Phosphorylation of signal transducer and activator of transcription 3 and induction of cyclooxygenase 2 were absent in the colon of DSS-fed ob/ob mice.
  
  
  CONCLUSIONS
  These results show that leptin represents a functional link between the endocrine and immune systems.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.forename: Hans Anton
authors.initials: HA
authors.lastname: Lehr
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D003106:Colon / Q000378:metabolism; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology; D016264:Dextran Sulfate; D004198:Disease Susceptibility; D004790:Enzyme Induction; D005260:Female; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007527:Isoenzymes / Q000378:metabolism; D020738:Leptin / Q000172:deficiency / Q000494:pharmacology / Q000502:physiology*; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012016:Reference Values; D050796:STAT3 Transcription Factor; D015534:Trans-Activators / Q000502:physiology; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D020738:Leptin; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases