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

To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. Male C57BL/6J mice were classified according to control or high fat diet (HFD) with or without PPAR-δ agonist (GW) over...

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Published in:World journal of gastroenterology : WJG Vol. 21; no. 45; pp. 12787 - 12799
Main Authors: Lee, Hyun Jung, Yeon, Jong Eun, Ko, Eun Jung, Yoon, Eileen L, Suh, Sang Jun, Kang, Keunhee, Kim, Hae Rim, Kang, Seoung Hee, Yoo, Yang Jae, Je, Jihye, Lee, Beom Jae, Kim, Ji Hoon, Seo, Yeon Seok, Yim, Hyung Joon, Byun, Kwan Soo
Format: Journal Article
Language:English
Published: United States 07.12.2015
Subjects:
Animals
Anti-Inflammatory Agents - pharmacology
Blood Glucose - drug effects
Blood Glucose - metabolism
Cytoprotection
Diet, High-Fat
Disease Models, Animal
Gene Expression Regulation
Hep G2 Cells
Hepatocytes - drug effects
Hepatocytes - metabolism
Hepatocytes - pathology
Humans
Inflammasomes - antagonists & inhibitors
Inflammasomes - genetics
Inflammasomes - metabolism
Inflammation Mediators - metabolism
Lipopolysaccharides
Liver - drug effects
Liver - metabolism
Liver - pathology
Male
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease - genetics
Non-alcoholic Fatty Liver Disease - metabolism
Non-alcoholic Fatty Liver Disease - pathology
Non-alcoholic Fatty Liver Disease - prevention & control
Oxidative Stress - drug effects
Palmitic Acid - toxicity
PPAR delta - agonists
PPAR delta - metabolism
Signal Transduction - drug effects
Thiazoles - pharmacology
Time Factors
Nucleotide-binding and oligomerization domain-like receptor
Inflammasome
Nonalcoholic fatty liver disease
Nonalcoholic steatohepatitis
Peroxisome proliferator-activated receptors delta
ISSN:2219-2840
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Summary:To evaluate the inflammasome activation and the effect of peroxisome proliferator-activated receptors (PPAR)-δ agonist treatment in nonalcoholic fatty liver disease (NAFLD) models. 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. 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. 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.
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ISSN:2219-2840
DOI:10.3748/wjg.v21.i45.12787