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.

Disease Annotations    
fatty liver disease  (IAGP,IEP,ISO)
Insulin Resistance  (IAGP,IEP,ISO)
obesity  (IAGP,IEP,ISO)

Gene-Chemical Interaction Annotations    
rosiglitazone  (EXP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
Adipor2  (adiponectin receptor 2)

Genes (Mus musculus)
Adipor2  (adiponectin receptor 2)

Genes (Homo sapiens)
ADIPOR2  (adiponectin receptor 2)

OLETF  (Otsuka Long-Evans Tokushima fatty)

Additional Information