Digestive Diseases and Sciences

, 56:2818

Adiponectin and Plant-Derived Mammalian Adiponectin Homolog Exert a Protective Effect in Murine Colitis

  • Violeta Arsenescu
  • Meena L. Narasimhan
  • Tuna Halide
  • Ray A. Bressan
  • Chiara Barisione
  • Donald A. Cohen
  • Willem J. S. de Villiers
  • Razvan Arsenescu
Original Article

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.

Keywords

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

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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Violeta Arsenescu
    • 1
    • 2
  • Meena L. Narasimhan
    • 3
  • Tuna Halide
    • 4
  • Ray A. Bressan
    • 3
    • 6
    • 7
  • Chiara Barisione
    • 5
  • Donald A. Cohen
    • 4
  • Willem J. S. de Villiers
    • 1
    • 2
  • Razvan Arsenescu
    • 1
    • 4
  1. 1.Division of Digestive Diseases and Nutrition, Microbiology, Immunology and Molecular GeneticsUniversity of Kentucky Medical CenterLexingtonUSA
  2. 2.Graduate Center for Nutritional SciencesUniversity of KentuckyLexingtonUSA
  3. 3.Plant Stress Genomics Research CenterKing Abdullah University of Science and TechnologyThuwalKingdom of Saudi Arabia
  4. 4.Microbiology, Immunology and Molecular GeneticsUniversity of KentuckyLexingtonUSA
  5. 5.Research Center of Cardiovascular BiologyUniversity of GenoaLiguriaItaly
  6. 6.Division of Applied Sciences, WCU programGyeongsang National UniversityJinjuSouth Korea
  7. 7.Departments of Horticulture and Landscape ArchitecturePurdue UniversityWest LafayetteUSA

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