scholarly journals Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: Impact of liver methylation of the peroxisome proliferator-activated receptor γ coactivator 1α promoter

Hepatology ◽  
2010 ◽  
Vol 52 (6) ◽  
pp. 1992-2000 ◽  
Author(s):  
Silvia Sookoian ◽  
Maria Soledad Rosselli ◽  
Carolina Gemma ◽  
Adriana L. Burgueño ◽  
Tomas Fernández Gianotti ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Epigenetic Regulation ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Disease Impact

scholarly journals The Mitochondrial Trigger in an Animal Model of Nonalcoholic Fatty Liver Disease

Genes ◽  
2021 ◽  
Vol 12 (9) ◽  
pp. 1439
Author(s):  
Guglielmina Chimienti ◽  
Antonella Orlando ◽  
Francesco Russo ◽  
Benedetta D’Attoma ◽  
Manuela Aragno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mitochondrial Oxidative Stress ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy’s decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD.

scholarly journals Elucidation of SIRT-1/PGC-1α-associated mitochondrial dysfunction and autophagy in nonalcoholic fatty liver disease

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Jiang ◽  
Duankai Chen ◽  
Qiming Gong ◽  
Qunqing Xu ◽  
Dong Pan ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Sirtuin 1 ◽  
Liver Fat ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver

Abstract Background Nonalcoholic fatty liver disease (NAFLD) can lead to chronic liver diseases associated with mitochondrial damages. However, the exact mechanisms involved in the etiology of the disease are not clear. Methods To gain new insights, the changes affecting sirtuin 1 (SIRT-1) during liver fat accumulation was investigated in a NAFLD mouse model. In addition, the in vitro research investigated the regulation operated by SIRT-1 on mitochondrial structures, biogenesis, functions, and autophagy. Results In mice NAFLD, high-fat-diet (HFD) increased body weight gain, upregulated serum total cholesterol, triglycerides, aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin levels, and liver malondialdehyde, and decreased liver superoxide dismutase activity. In liver, the levels of SIRT-1 and peroxisome proliferator-activated receptor-gamma coactivator -1α (PGC-1α) decreased. The expression of peroxisome proliferator-activated receptor-α and Beclin-1 proteins was also reduced, while p62/SQSTM1 expression increased. These results demonstrated SIRT-1 impairment in mouse NAFLD. In a well-established NAFLD cell model, exposure of the HepG2 hepatocyte cell line to oleic acid (OA) for 48 h caused viability reduction, apoptosis, lipid accumulation, and reactive oxygen species production. Disturbance of SIRT-1 expression affected mitochondria. Pre-treatment with Tenovin-6, a SIRT-1 inhibitor, aggravated the effect of OA on hepG2, while this effect was reversed by CAY10602, a SIRT-1 activator. Further investigation demonstrated that SIRT-1 activity was involved in mitochondrial biogenesis through PGC-1α and participated to the balance of autophagy regulatory proteins. Conclusion In conclusion, in high-fat conditions, SIRT-1 regulates multiple cellular properties by influencing on mitochondrial physiology and lipid autophagy via the PGC-1α pathway. The SIRT-1/PGC-1α pathway could be targeted to develop new NAFLD therapeutic strategies.

scholarly journals Fimasartan Ameliorates Nonalcoholic Fatty Liver Disease through PPARδ Regulation in Hyperlipidemic and Hypertensive Conditions

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Yong-Jik Lee ◽  
Yoo-Na Jang ◽  
Yoon-Mi Han ◽  
Hyun-Min Kim ◽  
Jong-Min Jeong ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Visceral Fat ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Protein Levels

To investigate the effects of fimasartan on nonalcoholic fatty liver disease in hyperlipidemic and hypertensive conditions, the levels of biomarkers related to fatty acid metabolism were determined in HepG2 and differentiated 3T3-L1 cells treated by high fatty acid and liver and visceral fat tissue samples of spontaneously hypertensive rats (SHRs) given high-fat diet. In HepG2 cells and liver tissues, fimasartan was shown to increase the protein levels of peroxisome proliferator-activated receptor delta (PPARδ), phosphorylated 5′ adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylated acetyl-CoA carboxylase (p-ACC), malonyl-CoA decarboxylase (MCD), medium chain acyl-CoA dehydrogenase (MCAD), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and it led to a decrease in the protein levels of 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSDH1), fatty acid synthase (FAS), and tumor necrosis factor-alpha (TNF-α). Fimasartan decreased lipid contents in HepG2 and differentiated 3T3-L1 cells and liver tissues. In addition, fimasartan increased the adiponectin level in visceral fat tissues. The antiadipogenic effects of fimasartan were offset by PPARδ antagonist (GSK0660). Consequently, fimasartan ameliorates nonalcoholic fatty liver disease mainly through the activation of oxidative metabolism represented by PPARδ-AMPK-PGC-1α pathway.

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