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Published on: March 11, 2017

Peroxisome proliferator-activated receptor agonist treatment of alcohol-induced hepatic insulin resistance

Suzanne M de la Monte1, Maoyin Pang, Rajeev Chaudhry

  • 1Liver Research Center and Departments of Medicine and Pathology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.

Hepatology Research : the Official Journal of the Japan Society of Hepatology
|March 24, 2011
PubMed
Abstract

Insights

Peroxisome-proliferator activated receptor (PPAR) agonists show promise in treating alcoholic hepatitis and insulin resistance. These PPAR agonists effectively reduced liver injury and improved insulin signaling in a rat model of chronic ethanol consumption.

Area of Science:

  • Hepatology
  • Endocrinology
  • Pharmacology

Background:

  • Chronic ethanol exposure leads to alcoholic hepatitis and hepatic insulin resistance.
  • Peroxisome-proliferator activated receptor (PPAR) agonists are known insulin sensitizers used in type 2 diabetes treatment.

Purpose of the Study:

  • To evaluate the therapeutic efficacy of PPAR agonists in mitigating alcoholic hepatitis and hepatic insulin resistance.
  • To investigate the effects of PPAR-α, PPAR-δ, and PPAR-γ agonists on liver injury and insulin signaling pathways in a chronic ethanol feeding model.

Main Methods:

  • Adult male rats were fed liquid diets with or without ethanol for 8 weeks.
  • Rats received vehicle or PPAR agonists (PPAR-α, PPAR-δ, PPAR-γ) via injection.
  • Liver tissues were analyzed for histopathology, gene expression, protein levels, and receptor binding.

Main Results:

  • Ethanol-induced liver injury included steatohepatitis, disrupted architecture, and apoptosis.
  • PPAR agonists reduced ethanol-mediated liver damage, architectural disarray, and steatosis.
  • PPAR-δ and PPAR-γ agonists improved insulin/IGF signaling and gene expression.

Conclusions:

  • PPAR agonists demonstrate potential in reducing chronic ethanol-induced liver injury.
  • PPAR agonists may alleviate hepatic insulin and IGF resistance, even with ongoing ethanol consumption.

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