scholarly journals Peroxisome Proliferator-Activated Receptors and Their Agonists in Nonalcoholic Fatty Liver Disease

2019 ◽  
Vol 9 (6) ◽  
pp. 731-739 ◽  
Author(s):  
Narendra S. Choudhary ◽  
Naveen Kumar ◽  
Ajay Duseja
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Nonalcoholic Fatty Liver ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Peroxisome proliferator-activated receptors alpha and gamma2 polymorphisms in nonalcoholic fatty liver disease: A study in Brazilian patients

Gene ◽  
2013 ◽  
Vol 529 (2) ◽  
pp. 326-331 ◽  
Author(s):  
Fernanda Aparecida Domenici ◽  
Maria José Franco Brochado ◽  
Ana de Lourdes Candolo Martinelli ◽  
Sergio Zucoloto ◽  
Selma Freire de Carvalho da Cunha ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Nonalcoholic Fatty Liver ◽  
Peroxisome Proliferator Activated Receptors

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 Effects of Pioglitazone on Nonalcoholic Fatty Liver Disease in the Absence of Constitutive Androstane Receptor Expression

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Hwa Young Ahn ◽  
Hwan Hee Kim ◽  
Ji-Yeon Hwang ◽  
Changhun Park ◽  
Bo Youn Cho ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Regulatory Element ◽  
Constitutive Androstane Receptor ◽  
Receptor Expression ◽  
Peroxisome Proliferator ◽  
Nonalcoholic Fatty Liver ◽  
Pioglitazone Treatment

Nonalcoholic fatty liver disease or steatohepatitis (NAFLD/NASH) is a fatty liver disease that is closely related to obesity, diabetes, and dyslipidemia. Pioglitazone, which was developed as an antidiabetic drug, is known to improve NALFD. Pioglitazone is metabolized by multiple cytochrome P450 (CYP) enzymes, which are regulated by the xenobiotic receptor constitutive androstane receptor (CAR). In this study, we investigated the effects of pioglitazone on NAFLD by absence of CAR activity under high-fat (HF)-fed conditions. CAR-/- mice showed significant improvement in NALFD after 12 weeks of pioglitazone treatment compared to wild-type mice. This improvement in NAFLD persisted in CAR-/- mice regardless of blood pioglitazone concentration. The expression of lipogenesis genes in the liver, sterol-regulatory element binding protein-1c (SREBP-1c), and stearoyl-CoA desaturase (SCD)-1 was decreased after pioglitazone treatment in HF-fed CAR-/- mice. In addition, the expression of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) was decreased by pioglitazone in HF-fed CAR-/- mice. Changes in SREBP-1c and PPAR γ2 remained constant over short-term (6 h) pioglitazone and lipid injection. Our results showed that NAFLD was improved significantly by pioglitazone in a CAR deletion state. These results might be valuable because they suggest that interaction with CAR and pioglitazone/PPARγ2 may be important in regulating gene expression associated with NAFLD.

scholarly journals Peroxisome Proliferator-Activated Receptor Genetic Polymorphisms and Nonalcoholic Fatty Liver Disease: Any Role in Disease Susceptibility?

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Paola Dongiovanni ◽  
Luca Valenti
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Peroxisome Proliferator ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
The Impact

Nonalcoholic fatty liver disease (NAFLD) defines a wide spectrum of liver diseases that extend from simple steatosis, that is, increased hepatic lipid content, to nonalcoholic steatohepatitis (NASH), a condition that may progress to cirrhosis with its associated complications. Nuclear hormone receptors act as intracellular lipid sensors that coordinate genetic networks regulating lipid metabolism and energy utilization. This family of transcription factors, in particular peroxisome proliferator-activated receptors (PPARs), represents attractive drug targets for the management of NAFLD and NASH, as well as related conditions such as type 2 diabetes and the metabolic syndrome. The impact on the regulation of lipid metabolism observed for PPARs has led to the hypothesis that genetic variants within the human PPARs genes may be associated with human disease such as NAFLD, the metabolic syndrome, and/or coronary heart disease. Here we review the available evidence on the association between PPARs genetic polymorphism and the susceptibility to NAFLD and NASH, and we provide a meta-analysis of the available evidence. The impact of PPAR variants on the susceptibility to NASH in specific subgroup of patients, and in particular on the response to therapies, especially those targeting PPARs, represents promising new areas of investigation.

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.

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