Peroxisome proliferator-activated receptor-delta agonist ameliorated inflammasome activation in nonalcoholic fatty liver disease.

Abstract

AIM:

To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models.

METHODS:

Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over period of 12 wk [control, HFD, HFD + lipopolysaccharide (LPS), HFD + LPS + GW group]. HepG2 cells were exposed to palmitic acid (PA) and/or LPS in the absence or presence of GW.

RESULTS:

HFD caused glucose intolerance and hepatic steatosis. In mice fed an HFD with LPS, caspase-1 and interleukin (IL)-1β in the liver were significantly increased. Treatment with GW ameliorated the steatosis and inhibited overexpression of pro-inflammatory cytokines. In HepG2 cells, PA and LPS treatment markedly increased mRNA of several nucleotide-binding and oligomerization domain-like receptor family members (NLRP3, NLRP6, and NLRP10), caspase-1 and IL-1β. PA and LPS also exaggerated reactive oxygen species production. All of the above effects of PA and LPS were reduced by GW. GW also enhanced the phosphorylation of AMPK-α.

CONCLUSION:

PPAR-δ agonist reduces fatty acid-induced inflammation and steatosis by suppressing inflammasome activation. Targeting the inflammasome by the PPAR-δ agonist may have therapeutic implication for NAFLD.

• Authors: Hyun Jung Lee, Jong Eun Yeon, Eun Jung Ko, Eileen L Yoon, Sang Jun Suh, Keunhee Kang, Hae Rim Kim, Seoung Hee Kang, Yang Jae Yoo, Jihye Je, Beom Jae Lee, Ji Hoon Kim, Yeon Seok Seo, Hyung Joon Yim, Kwan Soo Byun
• Journal: World journal of gastroenterology (World J Gastroenterol) Vol. 21 Issue 45 Pg. 12787-99 (Dec 07 2015) ISSN: 2219-2840 [Electronic] United States
• PMID: 26668503 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Blood Glucose
• GW 501516
• Inflammasomes
• Inflammation Mediators
• Lipopolysaccharides
• PPAR delta
• Thiazoles
• lipopolysaccharide, Escherichia coli O111 B4
• Palmitic Acid

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Blood Glucose (drug effects, metabolism)
• Cytoprotection
• Diet, High-Fat
• Disease Models, Animal
• Gene Expression Regulation
• Hep G2 Cells
• Hepatocytes (drug effects, metabolism, pathology)
• Humans
• Inflammasomes (antagonists & inhibitors, genetics, metabolism)
• Inflammation Mediators (metabolism)
• Lipopolysaccharides
• Liver (drug effects, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Non-alcoholic Fatty Liver Disease (genetics, metabolism, pathology, prevention & control)
• Oxidative Stress (drug effects)
• PPAR delta (agonists, metabolism)
• Palmitic Acid (toxicity)
• Signal Transduction (drug effects)
• Thiazoles (pharmacology)
• Time Factors