title: Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis.
abstract: BACKGROUND
  Hypoadiponectinemia has been associated with states of chronic inflammation in humans. Mesenteric fat hypertrophy and low adiponectin have been described in patients with Crohn's disease. We investigated whether adiponectin and the plant-derived homolog, osmotin, are beneficial in a murine model of colitis.
  
  
  METHODS
  C57BL/6 mice were injected (i.v.) with an adenoviral construct encoding the full-length murine adiponectin gene (AN+DSS) or a reporter-LacZ (Ctr and V+DSS groups) prior to DSS colitis protocol. In another experiment, mice with DSS colitis received either osmotin (Osm+DSS) or saline (DSS) via osmotic pumps. Disease progression and severity were evaluated using body weight, stool consistency, rectal bleeding, colon lengths, and histology. In vitro experiments were carried out in bone marrow-derived dendritic cells.
  
  
  RESULTS
  Mice overexpressing adiponectin had lower expression of proinflammatory cytokines (TNF, IL-1β), adipokines (angiotensin, osteopontin), and cellular stress and apoptosis markers. These mice had higher levels of IL-10, alternative macrophage marker, arginase 1, and leukoprotease inhibitor. The plant adiponectin homolog osmotin similarly improved colitis outcome and induced robust IL-10 secretion. LPS induced a state of adiponectin resistance in dendritic cells that was reversed by treatment with PPARγ agonist and retinoic acid.
  
  
  CONCLUSIONS
  Adiponectin exerted protective effects during murine DSS colitis. It had a broad activity that encompassed cytokines, chemotactic factors as well as processes that assure cell viability during stressful conditions. Reducing adiponectin resistance or using plant-derived adiponectin homologs may become therapeutic options in inflammatory bowel disease.
authors.affiliation: Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular Genetics, University of Kentucky Medical Center, Lexington, KY 40536, USA.
authors.forename: Violeta
authors.initials: V
authors.lastname: Arsenescu
authors.forename: Meena L
authors.initials: ML
authors.lastname: Narasimhan
authors.forename: Tuna
authors.initials: T
authors.lastname: Halide
authors.forename: Ray A
authors.initials: RA
authors.lastname: Bressan
authors.forename: Chiara
authors.initials: C
authors.lastname: Barisione
authors.forename: Donald A
authors.initials: DA
authors.lastname: Cohen
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
authors.forename: Razvan
authors.initials: R
authors.lastname: Arsenescu
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D054392:Adipokines / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D015316:Genetic Therapy; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010940:Plant Proteins / Q000627:therapeutic use*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; D052242:Adiponectin; D016207:Cytokines; D010940:Plant Proteins; C073139:osmotin protein, Nicotiana tabacum; D016264:Dextran Sulfate