Adiponectin and plant-derived mammalian adiponectin homolog exert a protective effect in murine colitis
Narasimhan, Meena L.
Bressan, Ray Anthony
Cohen, Donald A.
De Villiers, Willem Js S
Arsenescu, Razvan I.
KAUST DepartmentBiological and Environmental Sciences and Engineering (BESE) Division
Desert Agriculture Initiative
Online Publication Date2011-04-11
Print Publication Date2011-10
Permanent link to this recordhttp://hdl.handle.net/10754/561751
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AbstractBackground: 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. 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. © 2011 Springer Science+Business Media, LLC.
CitationArsenescu, V., Narasimhan, M. L., Halide, T., Bressan, R. A., Barisione, C., Cohen, D. A., … Arsenescu, R. (2011). Adiponectin and Plant-Derived Mammalian Adiponectin Homolog Exert a Protective Effect in Murine Colitis. Digestive Diseases and Sciences, 56(10), 2818–2832. doi:10.1007/s10620-011-1692-0
SponsorsThis work was supported by grants from Broad Medical Foundation, UCB Inc., Kentucky Science & Engineering Foundation (RA), and from NIH-DK07778-07 (VA). There are no competing financial interests to declare.
JournalDigestive Diseases and Sciences