RGD Reference Report - Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an animal model of nonalcoholic steatohepatitis. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Regulation of oxidative stress and inflammation by hepatic adiponectin receptor 2 in an animal model of nonalcoholic steatohepatitis.

Authors: Matsunami, Tokio  Sato, Yukita  Ariga, Satomi  Sato, Takuya  Kashimura, Haruka  Hasegawa, Yuki  Yukawa, Masayoshi 
Citation: Matsunami T, etal., Int J Clin Exp Pathol. 2010 May 22;3(5):472-81.
RGD ID: 21076282
Pubmed: PMID:20606728   (View Abstract at PubMed)
PMCID: PMC2897102   (View Article at PubMed Central)

The pathogenesis of nonalcoholic steatohepatitis (NASH) is not well understood; however, the progression of fatty liver to NASH has been linked to oxidative stress and lipid peroxidation in the liver, leading to inflammation. Although the adiponectin receptor 2 (AdipoR2) has been identified as a modulator of oxidative stress and inflammation in the liver, it remains unclear whether the receptor has hepatic antioxidant and anti-inflammatory effects in NASH. In this study, we used an animal model of NASH to examine hepatic AdipoR2. Obese fa/fa Zucker rats fed a high-fat and high-cholesterol (HFC) diet spontaneously developed fatty liver with inflammation and fibrosis, characteristic of NASH, after 4, 8, or 12 weeks of HFC diet consumption. AdipoR2 expression was significantly decreased, whereas the expression of genes related to NADPH oxidase complex were increased. As a result of the decrease in AdipoR2 expression, the mRNA expression of genes located downstream of AdipoR2, i.e., Cu-Zn superoxide dismutase (Cu-Zn SOD) and Mn-SOD, also decreased. Furthermore, the expression of genes related to inflammation was increased. Increased oxidative stress and inflammation by down-regulation of AdipoR2 may contribute to the progression of NASH. Thus, the AdipoR2 might be a crucially important regulator of hepatic oxidative stress and inflammation in NASH.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypercholesterolemia inducedIAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
metabolic dysfunction-associated steatohepatitis susceptibilityISOAdipor2 (Rattus norvegicus)21076282; 21076282mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis susceptibilityIEP 21076282; 21076282; 21076282mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis susceptibilityISOCcl2 (Rattus norvegicus)21076282; 21076282mRNA:increased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis susceptibilityIEP 21076282; 21076282; 21076282mRNA:increased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis susceptibilityISONox4 (Rattus norvegicus)21076282; 21076282mRNA:increased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis susceptibilityISOSod1 (Rattus norvegicus)21076282; 21076282mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis susceptibilityISOSod2 (Rattus norvegicus)21076282; 21076282mRNA:decreased expression:liver (rat)RGD 
metabolic dysfunction-associated steatohepatitis inducedIAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
metabolic dysfunction-associated steatohepatitis susceptibilityISOTnf (Rattus norvegicus)21076282; 21076282mRNA:increased expression:liver (rat)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
decreased catalase activity  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
decreased glutathione peroxidase activity  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
decreased superoxide dismutase level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased circulating alanine transaminase level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased circulating cholesterol level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased circulating free fatty acids level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased circulating glucose level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased circulating triglyceride level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased liver triglyceride level  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
increased liver weight  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
liver inflammation  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
oxidative stress  IAGPcontrolled fat content diet and controlled cholesterol content diet and controlled sodium content drinking water21076282compared to standard diet ratsRGD 
Objects Annotated

Genes (Rattus norvegicus)
Adipor2  (adiponectin receptor 2)
Ccl2  (C-C motif chemokine ligand 2)
Nox4  (NADPH oxidase 4)
Sod1  (superoxide dismutase 1)
Sod2  (superoxide dismutase 2)
Tnf  (tumor necrosis factor)

Genes (Mus musculus)
Adipor2  (adiponectin receptor 2)
Ccl2  (C-C motif chemokine ligand 2)
Nox4  (NADPH oxidase 4)
Sod1  (superoxide dismutase 1, soluble)
Sod2  (superoxide dismutase 2, mitochondrial)
Tnf  (tumor necrosis factor)

Genes (Homo sapiens)
ADIPOR2  (adiponectin receptor 2)
CCL2  (C-C motif chemokine ligand 2)
NOX4  (NADPH oxidase 4)
SOD1  (superoxide dismutase 1)
SOD2  (superoxide dismutase 2)
TNF  (tumor necrosis factor)

Strains
Slc:ZUC-Leprfa-/-  (Zucker fatty rats)


Additional Information