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.

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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Abbreviations

Ao:

Angiotensinogen

ACE:

Angiotensin converting enzyme

AN:

Adiponectin

AT1a:

Angiotensin receptor 1a

BIP:

Endoplasmic reticulum-binding protein (Hsp70)

CASP12:

Caspase 12

CCR2:

Chemokine (C–C motif), receptor2

CD14:

Cluster of differentiation 14

CHOP:

C/EBP homologous protein

COX2 :

Cyclooxygenase 2

DC:

Dendritic cells

DSS:

Dextran sodium sulfate

ER:

Endoplasmic reticulum

IBD:

Inflammatory bowel disease

IL10:

Interleukin 10

LPS:

Lipopolysaccharide

MCP1:

Monocyte chemotactic protein-1

NOD2:

Nucleotide-binding oligomerization domain containing 2

PCNA:

Proliferating cell nuclear antigen

PGE2:

prostaglandin E2

PPARΎ :

Peroxisome proliferator-activated receptor γ

P38MAPK:

p38 mitogen-activated protein kinase

SLPi:

Secretory leukoprotease inhibitor

Th1, 2:

T helper cell type 1, 2

TLR:

Toll-like receptor

TNFα:

Tumor necrosis factor α

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Acknowledgments

This 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.

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Correspondence to Razvan Arsenescu.

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Arsenescu, V., Narasimhan, M.L., Halide, T. et al. Adiponectin and Plant-Derived Mammalian Adiponectin Homolog Exert a Protective Effect in Murine Colitis. Dig Dis Sci 56, 2818 (2011). https://doi.org/10.1007/s10620-011-1692-0

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Keywords

  • Adiponectin
  • Inflammatory bowel disease
  • Mammalian adiponectin homolog
  • PPARγ agonists
  • Dendritic cells
  • Inflammatory bowel disease