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Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis.

Authors: Arsenescu, V  Narasimhan, ML  Halide, T  Bressan, RA  Barisione, C  Cohen, DA  De Villiers, WJ  Arsenescu, R 
Citation: Arsenescu V, etal., Dig Dis Sci. 2011 Oct;56(10):2818-32. Epub 2011 Apr 11.
Pubmed: (View Article at PubMed) PMID:21479819
DOI: Full-text: DOI:10.1007/s10620-011-1692-0

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-1beta), 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 PPARgamma agonist and retinoic acid. CONCLUSION: 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.

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CRRD Object Information
CRRD ID: 5686898
Created: 2012-01-31
Species: All species
Last Modified: 2012-01-31
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.