Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

Alwayn, Ian P. J.; Andersson, Charlotte; Lee, Sang; Arsenault, Danielle; Bistrian, Bruce R.; Gura, Kathleen M.; Nosé, Vânia; Zauscher, Blanca; Moses, Marsha A.; Puder, Mark

doi:10.1152/ajpgi.00047.2006

Cited by 30 publications

(26 citation statements)

References 69 publications

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“…Consequently, transcriptomic techniques may detect nutrimentinduced changes even when physiological parameters are not yet changed or have near-significant effects on more recognized markers. Previous research studies have demonstrated that n-3 PUFA can inhibit cytokine production by direct actions on the intracellular signaling pathways that lead to activation of one or more transcription factors such as PPARs [29,30] and NF-kB [1,31]. As mentioned above, both genders activated significantly the PPARA pathway after n-3 PUFA supplementation; however, only men significantly changed the NF-kB pathway.…”

Section: Discussionmentioning

confidence: 75%

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population

Rudkowska

Paradis

Thifault

et al. 2013

The Journal of Nutritional Biochemistry

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Section: Discussionmentioning

confidence: 75%

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population

Rudkowska

Paradis

Thifault

et al. 2013

The Journal of Nutritional Biochemistry

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“…ACOX1 is the key enzyme of peroxisomal β-oxidation, and lack of the gene results in hepatocytes that can't oxidize very long chain fatty acids and causes hepatic steatosis. PPARα agonist up-regulates the expression of CPT1 [42] and inhibits TNF-α and IL-6 levels [43,44]. AMPK activation increases fatty acid oxidation likely by activating PPARα [45] and CPT1 [46].…”

Section: Discussionmentioning

confidence: 99%

Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2 Cells

Zeng

Tang

Yin

et al. 2016

Cell Physiol Biochem

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Background: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model. Methods: This study was divided into four groups including Control group, Model group (FFA group), Alisol A 24-acetate (FFA+A) group, Fenofibrate (FFA+F) group. Preventive role of Alisol A 24-acetate was evaluated using 10µM Alisol A 24-acetate plus 1 mM FFA (oleate:palmitate=2:1) incubated with HepG2 cells for 24 h, which was determined by Oil Red O Staining, Oil Red O based colorimetric assay and intracellular triglyceride (TG) content. Besides, the inflammatory cytokines tumor necrosis factor (TNF)- α, interleukin (IL)-6 levels as well as the protein and mRNA expressions that were involved in fatty acid synthesis and oxidation including Adiponectin, AMP-activated protein kinase (AMPK) α, peroxisome proliferator-activated receptor (PPAR) α, sterol regulatory element binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1) and acyl coenzyme A oxidase 1 (ACOX1) were detected. Results: Alisol A 24-acetate significantly decreased the numbers of lipid droplets, Oil Red O lipid content, and intracellular TG content. Besides, inflammatory cytokines TNF-α, IL-6 levels were markedly inhibited by Alisol A 24-acetate. Furthermore, Alisol A 24-acetate effectively increased the protein and mRNA expressions of Adiponectin, the phosphorylation of AMPKα, CPT1 and ACOX1, whereas decreased SREBP-1c, the phosphorylation of ACC and FAS at both protein and mRNA levels. However, there was no significant effect on the protein and mRNA expressions of PPARα by Alisol A 24-acetate. Conclusions: These results demonstrated that Alisol A 24-acetate effectively ameliorated hepatic steatosis likely through Adiponectin, which activated AMPKα signaling pathways via down-regulating SREBP-1c, ACC, FAS and up-regulating CPT1 and ACOX1, and inhibited inflammation. Thereby, Alisol A 24-acetate could be a promising candidate for the treatment of NAFLD.

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“…It is noteworthy that PPAR␣ knockout (Ϫ/Ϫ) mice display severe hepatic steatosis upon fasting as a result of failure to up-regulate the fatty acid oxidation system (Ip et al, 2003) Proper activation of PPAR␣ is required to enhance hepatic lipid turnover to enable sufficient clearance of lipids from the liver, preventing lipid accumulation and peroxidation in murine NASH models system (Ip et al, 2003;Harano et al, 2006). Activity of PPAR␣ is enhanced by phosphorylation of serine residues S12 and S21 upon insulin treatment and impaired by high-fat diets, alcohol, and inflammation (Juge-Aubry et al, 1999;Galli et al, 2001;Nanji et al, 2004;Alwayn et al, 2006;Svegliati-Baroni et al, 2006).…”

Section: Roles For Saturated and Monounsaturated Fatty Acids In Nonalmentioning

confidence: 99%

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

Anderson

Borlak²

2008

Pharmacol Rev

341

255

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Inhibition of matrix metalloproteinases increases PPAR-α and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model

Abstract: . Inhibition of matrix metalloproteinases increases PPAR-␣ and IL-6 and prevents dietary-induced hepatic steatosis and injury in a murine model.

Cited by 30 publications

References 69 publications

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population

Transcriptomic and metabolomic signatures of an n-3 polyunsaturated fatty acids supplementation in a normolipidemic/normocholesterolemic Caucasian population

Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2 Cells

Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis

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