Adiponectin and Plant-Derived Mammalian Adiponectin Homolog Exert a Protective Effect in Murine Colitis
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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.
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.
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.
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.
KeywordsAdiponectin Inflammatory bowel disease Mammalian adiponectin homolog PPARγ agonists Dendritic cells Inflammatory bowel disease
Angiotensin converting enzyme
Angiotensin receptor 1a
Endoplasmic reticulum-binding protein (Hsp70)
Chemokine (C–C motif), receptor2
Cluster of differentiation 14
C/EBP homologous protein
Dextran sodium sulfate
Inflammatory bowel disease
Monocyte chemotactic protein-1
Nucleotide-binding oligomerization domain containing 2
Proliferating cell nuclear antigen
Peroxisome proliferator-activated receptor γ
p38 mitogen-activated protein kinase
Secretory leukoprotease inhibitor
- Th1, 2
T helper cell type 1, 2
Tumor necrosis factor α
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