RGD Reference Report - Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats. - Rat Genome Database

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Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats.

Authors: Li, Jia  Xue, Yao-Ming  Zhu, Bo  Pan, Yong-Hua  Zhang, Yan  Wang, Chunxia  Li, Yuhao 
Citation: Li J, etal., J Diabetes Res. 2018 Aug 27;2018:4627842. doi: 10.1155/2018/4627842. eCollection 2018.
RGD ID: 21406435
Pubmed: PMID:30225267   (View Abstract at PubMed)
PMCID: PMC6129789   (View Article at PubMed Central)
DOI: DOI:10.1155/2018/4627842   (Journal Full-text)

Rosiglitazone is an agonist of peroxisome proliferator-activated receptor- (PPAR-) γ that is principally associated with insulin action. The exact mechanisms underlying its insulin-sensitizing action are still not fully elucidated. It is well known that adiponectin mostly secreted in adipose tissue is an insulin sensitizer. Here, we found that treatment of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with rosiglitazone (3 mg/kg, once daily, by oral gavage for 33 weeks) attenuated the increase in fasting plasma insulin concentrations and the index of the homeostasis model assessment of insulin resistance along with the age growth and glucose concentrations during an oral glucose tolerance test. In addition, the increase in plasma alanine aminotransferase activity, concentrations of fasting plasma nonesterified fatty acids and triglyceride, and hepatic triglyceride content was also suppressed. The hepatic protein expression profile revealed that rosiglitazone increased the downregulated total protein expression of insulin receptor substrate 1 (IRS-1) and IRS-2. Furthermore, the treatment suppressed the upregulated phosphorylation of IRS-1 at Ser307 and IRS-2 at Ser731. The results indicate that rosiglitazone ameliorates hepatic and systemic insulin resistance, hepatic inflammation, and fatty liver. Mechanistically, rosiglitazone suppressed hepatic protein overexpression of both phosphorylated nuclear factor- (NF-) κBp65 and inhibitory-κB kinase-α/β, a transcription factor that primarily regulates chronic inflammatory responses and the upstream NF-κB signal transduction cascades which are necessary for activating NF-κB, respectively. More importantly, rosiglitazone attenuated the decreases in adipose adiponectin mRNA level, plasma adiponectin concentrations, and hepatic protein expression of adiponectin receptor-1 and receptor-2. Thus, we can draw the conclusion that rosiglitazone elicits an adiponectin-mediated insulin-sensitizing action at the adipose tissue-liver axis in obese rats. Our findings may provide new insights into the mechanisms of action of rosiglitazone.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADIPOR2HumanInsulin Resistance treatmentISOAdipor2 (Rattus norvegicus) RGD 
Adipor2MouseInsulin Resistance treatmentISOAdipor2 (Rattus norvegicus) RGD 
Adipor2RatInsulin Resistance treatmentIEP  RGD 
LETORatInsulin Resistance MODEL: controlIAGP compared to OLETF ratsRGD 
OLETFRatInsulin Resistance MODEL: treatmentIAGProsiglitazonecompared to LETO ratsRGD 
ADIPOR2Humanobesity treatmentISOAdipor2 (Rattus norvegicus) RGD 
Adipor2Mouseobesity treatmentISOAdipor2 (Rattus norvegicus) RGD 
Adipor2Ratobesity treatmentIEP  RGD 
LETORatobesity MODEL: controlIAGP compared to OLETF ratsRGD 
OLETFRatobesity MODEL: treatmentIAGProsiglitazonecompared to LETO ratsRGD 
ADIPOR2Humansteatotic liver disease treatmentISOAdipor2 (Rattus norvegicus) RGD 
Adipor2Mousesteatotic liver disease treatmentISOAdipor2 (Rattus norvegicus) RGD 
Adipor2Ratsteatotic liver disease treatmentIEP  RGD 
LETORatsteatotic liver disease MODEL: controlIAGP compared to OLETF ratsRGD 
OLETFRatsteatotic liver disease MODEL: treatmentIAGProsiglitazonecompared to LETO ratsRGD 

Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ADIPOR2Humanrosiglitazone increases expression ISOAdipor2 (Rattus norvegicus)rosiglitazone increases expression of adipor2 protein in liver of OLETF ratsRGD 
Adipor2Ratrosiglitazone increases expression EXP rosiglitazone increases expression of adipor2 protein in liver of OLETF ratsRGD 
Adipor2Mouserosiglitazone increases expression ISOAdipor2 (Rattus norvegicus)rosiglitazone increases expression of adipor2 protein in liver of OLETF ratsRGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OLETFRatabnormal adipose tissue amount  IAGP compared to LETO ratsRGD 
OLETFRatabnormal circulating alanine transaminase level  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatdecreased adiponectin level  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatdecreased circulating adiponectin level  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatimpaired glucose tolerance  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatincreased body weight  IAGP compared to LETO ratsRGD 
OLETFRatincreased circulating free fatty acids level  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatincreased circulating glucose level  IAGP compared to LETO ratsRGD 
OLETFRatincreased circulating insulin level  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatincreased circulating triglyceride level  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
OLETFRatincreased food intake  IAGP compared to LETO ratsRGD 
OLETFRatinsulin resistance  IAGP compared to LETO rats and OLETF rats treated with rosiglitazoneRGD 
Objects Annotated

Genes (Rattus norvegicus)
Adipor2  (adiponectin receptor 2)

Genes (Mus musculus)
Adipor2  (adiponectin receptor 2)

Genes (Homo sapiens)
ADIPOR2  (adiponectin receptor 2)

Strains
LETO  (NA)
OLETF  (Otsuka Long-Evans Tokushima fatty)


Additional Information