Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Zardi, Enrico Maria; Navarini, Luca; Sambataro, Gianluca; Piccinni, P; Sambataro, Fm; Spina, Catherine S.; Dobrina, Aldo

doi:10.2174/09298673113209990136

Cited by 76 publications

(52 citation statements)

References 284 publications

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“…We compared the F and S groups and observed that 166 genes were up-regulated and 244 genes were down-regulated. KEGG pathway analyses of the 410 differentially expressed genes indicated that many of the genes were enriched in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which is involved in lipid metabolism (Zardi et al, 2013) (Table 2). Genes involved in fatty acid oxidation (i.e., Glpk, Ubc, Cpt1, and Pgar) were up-regulated in the F group compared with the S group.…”

Section: Differential Gene Expression In the Two Groupsmentioning

confidence: 99%

Comparative transcriptomic analyses of two bighead carp ( Hypophthalmichthys nobilis ) groups with different growth rates

Wang

Feng

et al. 2016

Comparative Biochemistry and Physiology Part D: Genomics and Pr

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Section: Differential Gene Expression In the Two Groupsmentioning

confidence: 99%

Comparative transcriptomic analyses of two bighead carp ( Hypophthalmichthys nobilis ) groups with different growth rates

Wang

Feng

et al. 2016

Comparative Biochemistry and Physiology Part D: Genomics and Pr

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“…Apart from de novo expression of α-SMA, reduced PPAR-γ expression is also a marker for HSC activation (20,21). The results of the present study showed that POP inhibitor significantly decreased, while lentivirus-mediated overexpression of POP increased the expression of PPAR-γ.…”

Section: Discussionmentioning

confidence: 46%

“…Peroxisome proliferator activated receptor-γ (PPAR-γ) was initially identified as a key regulator of adipogenesis (19), while increasing evidence has confirmed that PPAR-γ is a key factor in HSC activation and phenotypic alteration, maintaining HSCs in a quiescent phase, and suppressing the production of type I collagen, α-SMA and TGF-β1. Thus, PPAR-γ has an important role in reducing and preventing liver fibrosis (20,21). PPAR-γ can disrupt the TGF-β signaling pathway and Smad-dependent promoter activity, directly antagonizes the activation and/or function of Smad3 in fibroblasts without affecting the protein expression of stimulatory Smad3.…”

Section: Introductionmentioning

confidence: 99%

Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-γ

Zhou

Wang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo with high activity in the liver. However, its biological functions in the liver have remained largely elusive. A previous study by our group has shown that POP produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was therefore hypothesized that POP may affect the activation state of HSCs and has an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate cell line was treated with the POP inhibitor S17092 or transfected with recombinant lentivirus to overexpress POP. Cell proliferation and apoptosis were determined using a Cell Counting Kit-8 and flow cytometry, respectively. The activation status of HSCs was determined by examination of the expression of α-smooth muscle actin (α-SMA), collagen I, monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF)-β-Smad signaling and peroxisome proliferator activated receptor-γ (PPAR-γ). Inhibition by S17092 decreased, whereas lentiviral expression increased the activity of POP and cell proliferation, while neither of the treatments affected cell apoptosis. Of note, S17092 significantly increased, whereas POP overexpression decreased the expression of α-SMA and MCP-1 without affecting the expression of collagen I and TGF-β1. Furthermore, S17092 caused a reduction, whereas POP overexpression caused an upregulation of Smad7 protein and PPAR-γ, but not phosphorylated-Smad2/3 expression. In conclusion, POP attenuated the activation of HSCs through inhibition of TGF-β signaling and induction of PPAR-γ, which may have therapeutic potential in liver fibrosis.

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“…Pparg regulates adipogenesis, lipid metabolism and insulin sensitivity [22,23]. Pparg presents two promoter regions [24].…”

Section: Discussionmentioning

confidence: 99%

“…PPARs are ligand-dependent transcription factors that regulate target gene expression by binding to a PPAR at regulatory sites [22,23]. The PPAR gamma gene Pparg presents splicing variants with two protein isoforms (PPARG1 and PPARG2) and two promoter regions [24,25].…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

et al. 2014

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Background/Aims: To investigate the global changes in DNA methylation and methylation of the promoter region of the peroxisome proliferator-activated receptor gamma transcript variant 2 (Pparg2) gene resulting from a high-fat diet (HFD) and/or fish oil supplementation. Methods: Fish oil, rich in omega-3 polyunsaturated fatty acids, or water was orally administered to male mice for 12 weeks. After the first 4 weeks, the animals were fed a control diet or an HFD until the end of the experimental protocol, when the epididymal fat, gastrocnemius muscle and liver were excised. Results:Pparg2 mRNA expression was upregulated by obesity and downregulated by fish oil supplementation in the liver. In the gastrocnemius muscle, diet-induced obesity increased global DNA methylation. Fish oil prevented the decrease in Pparg2 promoter methylation induced by obesity in the gastrocnemius muscle. Regardless of the diet given, fish oil supplementation increased Pparg2 promoter methylation at CpG-263 in muscle and adipose tissue. Conclusion: HFD and fish oil modified global and Pparg2 promoter DNA methylation in a tissue-specific manner. Fish oil supplementation attenuated body weight gain, abolished the increase in Pparg2 expression in the liver and prevented the decrease in Pparg2 promoter methylation in the muscle induced by the HFD.

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Hepatic PPARs: Their Role in Liver Physiology, Fibrosis and Treatment

Cited by 76 publications

References 284 publications

Comparative transcriptomic analyses of two bighead carp ( Hypophthalmichthys nobilis ) groups with different growth rates

Comparative transcriptomic analyses of two bighead carp ( Hypophthalmichthys nobilis ) groups with different growth rates

Prolyl oligopeptidase attenuates hepatic stellate cell activation through induction of Smad7 and PPAR-γ

DNA Methylation Changes Induced by a High-Fat Diet and Fish Oil Supplementation in the Skeletal Muscle of Mice

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