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Role of peroxisome proliferators-activated receptors in the pathogenesis and treatment of nonalcoholic fatty liver disease 被引量:34
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作者 Eric R Kallwitz Alan McLachlan Scott J Cotler 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第1期22-28,共7页
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of ... Nonalcoholic fatty liver disease (NAFLD) is highly prevalent and can result in nonalcoholic steatohepatitis (NASH) and progressive liver disease including cirrhosis and hepatocellular carcinoma. A growing body of literature implicates the peroxisome proliferators- activated receptors (PPARs) in the pathogenesis and treatment of NAFLD. These nuclear hormone receptors impact on hepatic triglyceride accumulation and insulin resistance. The aim of this review is to describe the data linking PPARα and PPART to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH. 展开更多
关键词 Non-alcoholic fatty liver disease peroxisome proliferators-activated receptors Insulin resiatance Metabolic syndrome Pharmacologic ligands
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Peroxisome proliferator-activated receptor agonists:A new hope towards the management of alcoholic liver disease
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作者 Siva Sundara Kumar Durairajan Abhay Kumar Singh Ashok Iyaswamy 《World Journal of Gastroenterology》 SCIE CAS 2024年第35期3965-3971,共7页
In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the inte... In this editorial,we examine a paper by Koizumi et al,on the role of peroxisome proliferator-activated receptor(PPAR)agonists in alcoholic liver disease(ALD).The study determined whether elafibranor protected the intestinal barrier and reduced liver fibrosis in a mouse model of ALD.The study also underlines the role of PPARs in intestinal barrier function and lipid homeostasis,which are both affected by ALD.Effective therapies are necessary for ALD because it is a critical health issue that affects people worldwide.This editorial analyzes the possibility of PPAR agonists as treatments for ALD.As key factors of inflammation and metabolism,PPARs offer multiple methods for managing the complex etiology of ALD.We assess the abilities of PPARα,PPARγ,and PPARβ/δagonists to prevent steatosis,inflammation,and fibrosis due to liver diseases.Recent research carried out in preclinical and clinical settings has shown that PPAR agonists can reduce the severity of liver disease.This editorial discusses the data analyzed and the obstacles,advantages,and mechanisms of action of PPAR agonists for ALD.Further research is needed to understand the efficacy,safety,and mechanisms of PPAR agonists for treating ALD. 展开更多
关键词 Alcoholic liver disease peroxisome proliferator-activated receptors peroxisome proliferator-activated receptors agonists Liver fibrosis INFLAMMATION Metabolic regulation HEPATOPROTECTION
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Dual peroxisome proliferator-activated receptorα/δagonists:Hope for the treatment of alcohol-associated liver disease?
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作者 Xin-Yang Zhang Qin-Jun-Jie Chen +2 位作者 Feng Zhu Min Li Dan Shang 《World Journal of Gastroenterology》 SCIE CAS 2024年第37期4163-4167,共5页
In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcoho... In this letter,we review the article“Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease”.We focus specifically on the detrimental effects of alcohol-associated liver disease(ALD)on human health.Given its insidious onset and increasing incidence,increasing awareness of ALD can contribute to reducing the prevalence of liver diseases.ALD comprises a spectrum of several different disorders,including liver steatosis,steatohepatitis,fibrosis,cirrhosis,and hepatocellular carcinoma.The pathogenesis of ALD is exceedingly complex.Previous studies have shown that peroxisome proliferator-activated receptors(PPARs)regulate lipid metabolism,glucose homeostasis and inflammatory responses within the organism.Additionally,their dysfunction is a major contributor to the progression of ALD.Elafibranor is an oral,dual PPARαandδagonist.The effectiveness of elafibranor in the treatment of ALD remains unclear.In this letter,we emphasize the harm of ALD and the burden it places on society.Furthermore,we summarize the clinical management of all stages of ALD and present new insights into its pathogenesis and potential therapeutic targets.Additionally,we discuss the mechanisms of action of PPARαandδagonists,the significance of their antifibrotic effects on ALD and future research directions. 展开更多
关键词 Alcohol-associated liver disease FIBROSIS Antifibrotic effect Elafibranor peroxisome proliferator-activated receptor
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Peroxisome proliferator-activated receptors as targets to treat metabolic diseases:Focus on the adipose tissue,liver,and pancreas
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作者 Henrique Souza-Tavares Carolline Santos Miranda +5 位作者 Isabela Macedo Lopes Vasques-Monteiro Cristian Sandoval Daiana Araujo Santana-Oliveira Flavia Maria Silva-Veiga Aline Fernandes-da-Silva Vanessa Souza-Mello 《World Journal of Gastroenterology》 SCIE CAS 2023年第26期4136-4155,共20页
The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs d... The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its comorbidities.The adipose tissue is the initial site of obesity impairments.During excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs.The pancreas is one of the organs most affected by obesity.Once lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long term.As for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic steatosis.This silent disease affects around 30%of the worldwide population and can evolve into end-stage liver disease.Although therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM management.Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation.This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling. 展开更多
关键词 OBESITY Insulin resistance peroxisome proliferator-activated receptors PANCREAS Hepatic steatosis Adipose tissue
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Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease 被引量:30
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作者 Vettickattuparambil George Giby Thekkuttuparambil Ananthanarayanan Ajith 《World Journal of Hepatology》 CAS 2014年第8期570-579,共10页
Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabe... Intrahepatic fat deposition has been demonstrated in patients with nonalcoholic fatty liver disease(NAFLD). Genetic and environmental factors are important for the development of NAFLD. Diseases such as obesity, diabetes, and hypertension have been found to be closely associated with the incidence of NAFLD. Evi-dence suggests that obesity and insulin resistance are the major factors that contribute to the development of NAFLD. In comparing the factors that contribute to the buildup of excess calories in obesity, an imbalance of energy homeostasis can be considered as the basis. Among the peripheral signals that are generated to regulate the uptake of food, signals from adipose tissue are of major relevance and involve the maintenance of energy homeostasis through processes such as lipo-genesis, lipolysis, and oxidation of fatty acids. Advances in research on adipose tissue suggest an integral role played by adipokines in NAFLD. Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transform-ing growth factor-β, and interleukin-6, are implicated in NAFLD. Other adipokines, such as leptin and adiponectin and, to a lesser extent, resistin and retinol binding protein-4 are also involved. Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription fac-tors, namely peroxisome proliferator-activated receptor(PPAR)-α. Recent studies have proposed downregula-tion of PPAR-α in cases of hepatic steatosis. This re-view discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD. 展开更多
关键词 NONALCOHOLIC FATTY liver disease ADIPOSE tissue Energy HOMEOSTASIS peroxisome proliferator activated receptors ADIPOKINES
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Peroxisome proliferator-activated receptors as targets to treat non-alcoholic fatty liver disease 被引量:21
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作者 Vanessa Souza-Mello 《World Journal of Hepatology》 CAS 2015年第8期1012-1019,共8页
Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcr... Lately, the world has faced tremendous progress in the understanding of non-alcoholic fatty liver disease(NAFLD) pathogenesis due to rising obesity rates. Peroxisome proliferator-activated receptors(PPARs) are transcription factors that modulate the expression of genes involved in lipid metabolism, energy homeostasis and inflammation, being altered in diet-induced obesity. Experimental evidences show that PPAR-alpha is the master regulator of hepatic beta-oxidation(mitochondrial and peroxisomal)and microsomal omega-oxidation, being markedly decreased by high-fat(HF) intake. PPAR-beta/delta is crucial to the regulation of forkhead box-containing protein O subfamily-1 expression and, hence, the modulation of enzymes that trigger hepatic gluconeogenesis. In addition, PPAR-beta/delta can activate hepatic stellate cells aiming to the hepatic recovery from chronic insult. On the contrary, PPAR-gamma upregulation by HF diets maximizes NAFLD through the induction of lipogenic factors, which are implicated in the fatty acid synthesis. Excessive dietary sugars also upregulate PPAR-gamma, triggering de novo lipogenesis and the consequent lipid droplets deposition within hepatocytes. Targeting PPARs to treat NAFLD seems a fruitful approach as PPAR-alpha agonist elicits expressive decrease in hepatic steatosis by increasing mitochondrial beta-oxidation, besides reduced lipogenesis. PPAR-beta/delta ameliorates hepatic insulin resistance by decreasing hepatic gluconeogenesis at postprandial stage. Total PPAR-gamma activation can exert noxious effects by stimulating hepatic lipogenesis. However, partial PPAR-gamma activation leads to benefits, mainly mediated by increased adiponectin expression and decreased insulin resistance. Further studies are necessary aiming at translational approaches useful to treat NAFLD in humans worldwide by targeting PPARs. 展开更多
关键词 peroxisome proliferator-activated receptors Non-alcoholic FATTY liver disease Obesity Treatment Insulin resistance BETA-OXIDATION LIPOGENESIS
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Peroxisome proliferator-activated receptors for hypertension 被引量:19
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作者 Daisuke Usuda Tsugiyasu Kanda 《World Journal of Cardiology》 CAS 2014年第8期744-754,共11页
Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and ... Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear receptor superfamily, which is composed of four members encoded by distinct genes(α, β, γ, and δ). The genes undergo transactivation or transrepression under specific mechanisms that lead to the induction or repression of target gene expression. As is the case with other nuclear receptors, all four PPAR isoforms contain five or six structural regions in four functional domains; namely, A/B, C, D, and E/F. PPARs have many functions, particularly functions involving control of vascular tone, inflammation, and energy homeostasis, and are, therefore, important targets for hypertension, obesity, obesity-induced inflammation, and metabolic syndrome in general. Hence, PPARs also represent drug targets, and PPARα and PPARγ agonists are used clinically in the treatment of dyslipidemia and type 2 diabetes mellitus, respectively. Because of their pleiotropic effects, they have been identified as active in a number of diseases and are targets for the development of a broad range of therapies for a variety of diseases. It is likely that the range of PPARγ agonist therapeutic actions will result in novel approaches to lifestyle and other diseases. The combination of PPARs with reagents or with other cardiovascular drugs, such as diuretics and angiotensin Ⅱ receptor blockers, should be studied.This article provides a review of PPAR isoform characteristics, a discussion of progress in our understanding of the biological actions of PPARs, and a summary of PPAR agonist development for patient management. We also include a summary of the experimental and clinical evidence obtained from animal studies and clinical trials conducted to evaluate the usefulness and effectiveness of PPAR agonists in the treatment of lifestyle-related diseases. 展开更多
关键词 peroxisome proliferator-activated receptors Nuclear receptor ISOFORM MRNA Blood pressure HYPERTENSION OBESITY Angiotensin II receptor blocker Diabetes mellitus
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THE INCREASE IN PLASMINOGEN ACTIVATOR INHIBITOR TYPE-1 EXPRESSION BY STIMULATION OF ACTIVATORS FOR PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS IN HUMAN ENDOTHELIAL CELLS 被引量:5
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作者 叶平 胡晓晖 赵亚力 《Chinese Medical Sciences Journal》 CAS CSCD 2002年第2期112-116,共5页
Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the pos... Objective.To investigate the effect of peroxis ome proliferator-activated recept ors(PPARs )activators on plasminogen activator inhibitor ty pe-1(PAI-1)expression in human umbilical vein e ndothelial cells and the possi-ble mechanism.Methods.Human umbilical vein endothelial ce lls(HUVECs )were obtained from normal fetus,and cul-tured conventionally.Then the HUVECs were exposed to test agents(linolenic acid,linoleic acid,oleic acid,stearic acid and prostaglandin J 2 respectively)in varying concentrations with fresh media.RT -PCR and ELISA were applied to determine the expression of PPARs and PAI-1in HUVECs.Results.PPARα,PPARδand PPARγmRNA were detected by using RT-PCR in HUVECs.Treatment of HUVECs with PPARαand PPARγactivators---linolenic acid,linoleic acid,oleic acid and prostaglandin J 2 respectively,but not with stearic a cid could augment PAI-I mRNA expression and protein secretion in a concentration-dependent manner.However,the mRNA expressions of 3subclasses of PPAR with their activators in HUVECs were not changed compared w ith controls.Conclusion.HUVECs express PPARs.PPARs activators may increase PAI-1expression in ECs,but the underlying mechanism remains uncle ar.Although PPARs expression was not enhanced after stimulated by their activators in ECs,the role of functionally active PPARs in regulating PA I-1expression in ECs needs to be further investigated by using transient gen e transfection assay. 展开更多
关键词 peroxisome proliferator-activate d receptors plasminogen activator inhibitor type-1 EXPRESSION endothelial cells
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An innovative approach for the treatment of Alzheimer's disease: the role of peroxisome proliferator-activated receptors and their ligands in development of alternative therapeutic interventions 被引量:3
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作者 Luca Piemontese 《Neural Regeneration Research》 SCIE CAS CSCD 2019年第1期43-45,共3页
Alzheimer's disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment... Alzheimer's disease is a multifactorial pathology, for which no cure is currently available. Nowadays, researchers are moving towards a new hypothesis of the onset of the illness, linking it to a metabolic impairment, q-his innovative approach will lead to the identification of new targets for the preparation of new effective drugs. Peroxisome proliferator-activated receptors and their ligands are the ideal candidates to reach the necessary breakthrough to defeat this complicate disease. 展开更多
关键词 Alzheimer's disease multifunctional drugs peroxisome proliferator-activated receptors type 3 diabetes innovative therapies type 2 diabetes mellitus METABOLISM NEUROINFLAMMATION
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Peroxisome-proliferator-activated receptors regulate redox signaling in the cardiovascular system 被引量:14
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作者 Teayoun Kim Qinglin Yang 《World Journal of Cardiology》 CAS 2013年第6期164-174,共11页
Peroxisome-proliferator-activated receptors(PPARs) comprise three subtypes(PPARα,δ and γ) to form a nuclear receptor superfamily.PPARs act as key transcriptional regulators of lipid metabolism,mitochondrial biogene... Peroxisome-proliferator-activated receptors(PPARs) comprise three subtypes(PPARα,δ and γ) to form a nuclear receptor superfamily.PPARs act as key transcriptional regulators of lipid metabolism,mitochondrial biogenesis,and anti-oxidant defense.While their roles in regulating lipid metabolism have been well established,the role of PPARs in regulating redox activity remains incompletely understood.Since redox activity is an integral part of oxidative metabolism,it is not surprising that changes in PPAR signaling in a specific cell or tissue will lead to alteration of redox state.The effects of PPAR signaling are directly related to PPAR expression,protein activities and PPAR interactions with their coregulators.The three subtypes of PPARs regulate cellular lipid and energy metabolism in most tissues in the body with overlapping and preferential effects on different metabolic steps depending on a specific tissue.Adding to the complexity,specific ligands of each PPAR subtype may also display different potencies and specificities of their role on regulating the redox pathways.Moreover,the intensity and extension of redoxregulation by each PPAR subtype are varied depending on different tissues and cell types.Both beneficial and adverse effects of PPAR ligands against cardiovascular disorders have been extensively studied by many groups.The purpose of the review is to summarize the effects of each PPAR on regulating redox and the underlying mechanisms,as well as to discuss the implications in the cardiovascular system. 展开更多
关键词 peroxisome-proliferator-activated receptor Redox CARDIOVASCULAR DISORDERS OXIDATIVE stress ANTIOXIDANT
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Role of peroxisome proliferator-activated receptors alpha and gamma in gastric ulcer: An overview of experimental evidences 被引量:1
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作者 Lekha Saha 《World Journal of Gastrointestinal Pharmacology and Therapeutics》 CAS 2015年第4期120-126,共7页
Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARα, PPARβ/δ, and PPARγ, have been identifieds... Peroxisome proliferator-activated receptors(PPARs) are ligand-activated transcription factors belonging to the nuclear hormone receptor superfamily. Three subtypes, PPARα, PPARβ/δ, and PPARγ, have been identifiedso far. PPARα is expressed in the liver, kidney, small intestine, heart, and muscle, where it activates the fatty acid catabolism and control lipoprotein assembly in response to long-chain unsaturated fatty acids, eicosanoids, and hypolipidemic drugs(e.g., fenofibrate). PPARβ/δ is more broadly expressed and is implicated in fatty acid oxidation, keratinocyte differentiation, wound healing, and macrophage response to very low density lipoprotein metabolism. This isoform has been implicated in transcriptional-repression functions and has been shown to repress the activity of PPARα or PPARγ target genes. PPARγ1 and γ2 are generated from a single-gene peroxisome proliferator-activated receptors gamma by differential promoter usage and alternative splicing. PPARγ1 is expressed in colon, immune system(e.g., monocytes and macrophages), and other tissues where it participates in the modulation of inflammation, cell proliferation, and differentiation. PPARs regulate gene expression through distinct mechanisms: Liganddependent transactivation, ligand-independent repression, and ligand-dependent transrepression. Studies in animals have demonstrated the gastric antisecretory activity of PPARα agonists like ciprofibrate, bezafibrate and clofibrate. Study by Pathak et al also demonstrated the effect of PPARα agonist, bezafibrate, on gastric secretion and gastric cytoprotection in various gastric ulcer models in rats. The majority of the experimental studies is on pioglitazone and rosiglitazone, which are PPARγ activators. In all the studies, both the PPARγ activators showed protection against the gastric ulcer and also accelerate the ulcer healing in gastric ulcer model in rats. Therefore, PPARα and PPARγ may be a target for gastric ulcer therapy. Finally, more studies are also needed to confirm the involvement of PPARs α and γ in gastric ulcer. 展开更多
关键词 peroxisome proliferator-activated receptors Gastri
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Role of peroxisome proliferator-activated receptors gene polymorphisms in type 2 diabetes and metabolic syndrome 被引量:10
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作者 Chen Dong Hui Zhou +4 位作者 Chong Shen Lu-Gang Yu Yi Ding Yong-Hong Zhang Zhi-Rong Guo 《World Journal of Diabetes》 SCIE CAS 2015年第4期654-661,共8页
Metabolic syndrome(MetS) and type 2 diabetes mellitus(T2DM) are the serious public health problems worldwide.Moreover,it is estimated that MetS patients have about five-fold greater risk of the T2 DM development compa... Metabolic syndrome(MetS) and type 2 diabetes mellitus(T2DM) are the serious public health problems worldwide.Moreover,it is estimated that MetS patients have about five-fold greater risk of the T2 DM development compared with people without the syndrome.Peroxisome proliferator-activated receptors are a subgroup of the nuclear hormone receptor superfamily of ligand-activated transcription factors which play an important role in the pathogenesis of MetS and T2 DM.All three members of the peroxisome proliferator-activated receptor(PPAR) nuclear receptor subfamily,PPARα,PPARp/5 and PPARγ are critical in regulating insulin sensitivity,adipogenesis,lipid metabolism,and blood pressure.Recently,more and more studies indicated that the gene polymorphism of PPARs,such as Leu^(162)Val and Val^(227)Ala of PPARα,+294T> C of PPARβ/δ,Pro^(12)Ala and C1431 T of PPARγ,are significantly associated with the onset and progressing of MetS and T2 DM in different population worldwide.Furthermore,a large body of evidence demonstrated that the glucose metabolism and lipid metabolism were influenced by gene-gene interaction among PPARs genes.However,given the complexity pathogenesis of metabolic disease,it is unlikely that genetic variation of a single locus would provide an adequate explanation of inter-individual differences which results in diverse clinical syndromes.Thus,gene-gene interactions and gene-environment interactions associated with T2 DM and MetS need future comprehensive studies. 展开更多
关键词 POLYMORPHISMS METABOLIC syndrome Type2 diabetes MELLITUS peroxisome proliferator-activatedreceptors
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The interplay between non-esterified fatty acids and bovine peroxisome proliferator-activated receptors: results of an in vitro hybrid approach
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作者 Sebastiano Busato Massimo Bionaz 《Journal of Animal Science and Biotechnology》 SCIE CAS CSCD 2021年第1期292-304,共13页
Background: In dairy cows circulating non-esterified fatty acids(NEFA) increase early post-partum while liver and other tissues undergo adaptation to greater lipid metabolism, mainly regulated by peroxisome proliferat... Background: In dairy cows circulating non-esterified fatty acids(NEFA) increase early post-partum while liver and other tissues undergo adaptation to greater lipid metabolism, mainly regulated by peroxisome proliferator-activated receptors(PPAR). PPAR are activated by fatty acids(FA), but it remains to be demonstrated that circulating NEFA or dietary FA activate bovine PPAR. We hypothesized that circulating NEFA and dietary FA activate PPAR in dairy cows.Methods: The dose-response activation of PPAR by NEFA or dietary FA was assessed using HP300 e digital dispenser and luciferase reporter in several bovine cell types. Cells were treated with blood plasma isolated from Jersey cows before and after parturition, NEFA isolated from the blood plasma, FA released from lipoproteins using milk lipoprotein lipase(LPL), and palmitic acid(C16:0). Effect on each PPAR isotype was assessed using specific synthetic inhibitors.Results: NEFA isolated from blood serum activate PPAR linearly up to ~ 4-fold at 400 μmol/L in MAC-T cells but had cytotoxic effect. Addition of albumin to the culture media decreases cytotoxic effects of NEFA but also PPAR activation by ~ 2-fold. Treating cells with serum from peripartum cows reveals that much of the PPAR activation can be explained by the amount of NEFA in the serum(R~2 = 0.91) and that the response to serum NEFA follows a quadratic tendency, with peak activation around 1.4 mmol/L. Analysis of PPAR activation by serum in MAC-T, BFH-12 and BPAEC cells revealed that most of the activation is explained by the activity of PPARδ and PPARγ, but not PPARα. Palmitic acid activated PPAR when added in culture media or blood serum but the activation was limited to PPARδ and PPARα and the response was nil in serum from post-partum cows. The addition of LPL to the serum increased > 1.5-fold PPAR activation.Conclusion: Our results support dose-dependent activation of PPAR by circulating NEFA in bovine, specifically δand γ isotypes. Data also support the possibility of increasing PPAR activation by dietary FA;however, this nutrigenomics approach maybe only effective in pre-partum but not post-partum cows. 展开更多
关键词 ALBUMIN Blood serum BOVINE Gene reporter HEPATOCYTES Lipoprotein lipase Mammary cells Non-esterified fatty acids peroxisome proliferator-activated receptor
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Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus 被引量:13
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作者 Ai-Qin Song Li-Rong Sun +2 位作者 Yan-Xia Zhao Yan-Hua Gao Lei Chen 《Asian Pacific Journal of Tropical Medicine》 SCIE CAS 2016年第1期89-93,共5页
Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes m... Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats. 展开更多
关键词 INSULIN METFORMIN Gestational diabetes mellitus peroxisome proliferator-activated receptor γ coactivator-1 A METHYLATION GLYCOLIPID metabolism
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Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 in patients with fatty liver diseases 被引量:11
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作者 Johannes W Rey Andrea Noetel +6 位作者 Aline Hardt Ali Canbay Hakan Alakus Axel zur Hausen Hans Peter Dienes Uta Drebber Margarete Odenthal 《World Journal of Gastroenterology》 SCIE CAS CSCD 2010年第46期5830-5837,共8页
AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD... AIM:To test the occurrence of the Pro12Ala mutation of the peroxisome proliferator-activated receptor-γ (PPARγ)2-gene in patients with non-alcoholic fatty liver disease (NAFLD) or alcoholic fatty liver disease (AFLD).METHODS:DNA from a total of 622 specimens including 259 blood samples of healthy blood donors and 363 histologically categorized liver biopsies of patients with NAFLD (n=263) and AFLD (n=100) were analyzed by Real-time polymerase chain reaction using allele-specific probes.RESULTS:In the NAFLD and the AFLD collective,3% of the patients showed homozygous occurrence of the Ala12 PPARγ2-allele,differing from only 1.5% cases in the healthy population.In NAFLD patients,a high incidence of the Ala12 mutant was not associated with the progression of fatty liver disease.However,we observed a significantly higher risk (odds ratio=2.50,CI:1.05-5.90,P=0.028) in AFLD patients carrying the mutated Ala12 allele to develop inflammatory alterations.The linkage of the malfunctioning Ala12-positive PPARγ2 isoform to an increased risk in patients with AFLD to develop severe steatohepatitis and fibrosis indicates a more prominent anti-inflammatory impact of PPARγ2 in progression of AFLD than of NAFLD.CONCLUSION:In AFLD patients,the Pro12Ala single nuclear polymorphism should be studied more extensively in order to serve as a novel candidate in biomarker screening for improved prognosis. 展开更多
关键词 Single NUCLEOTIDE polymorphism peroxisome proliferator-activated receptor γ Non-alcoholic STEATOHEPATITIS ALCOHOLIC STEATOHEPATITIS Inflammation FIBROSIS Hepatitis STEATOSIS STEATOHEPATITIS
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Peroxisome proliferator-activated receptor gamma inhibits hepatic fibrosis in rats 被引量:18
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作者 ZhengWang,Jia-Peng Xu,Yong-Chao Zheng,Wei Chen,Yong-Wei Sun,Zhi-YongWu and Meng Luo Department of General Surgery,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai 200127,China 《Hepatobiliary & Pancreatic Diseases International》 SCIE CAS 2011年第1期64-71,共8页
BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activa... BACKGROUND:Hepatic fibrosis is a necessary step in the development of hepatic cirrhosis.In this study we used lentiviral vector-mediated transfection technology to evaluate the effect of peroxisome proliferator-activated receptor gamma(PPAR-γ) on rat hepatic fibrosis. METHODS:Hepatic fibrosis in rats was induced by CCl4 for 2 weeks(early fibrosis)and 8 weeks(sustained fibrosis).The rats were randomly divided into four groups:normal control, fibrosis,blank vector,and PPAR-γ.They were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene by portal vein injection.The liver of the rats was examined histologically and hydroxyproline was assessed.In vitro primary hepatic stellate cells(HSCs)were infected with the recombinant lentiviral expression vector carrying the rat PPAR-γgene.The status of HSC proliferation was measured by the MTT assay.The protein levels of PPAR-γ,α-smooth muscle actin(α-SMA)and type I collagen expression were evaluated by the Western blotting method. RESULTS:In vitro studies revealed that expression of PPAR-γ inhibited expression ofα-SMA and type I collagen in activated HSCs(P<0.01)as well as HSC proliferation(P<0.01).In vivo experiments indicated that in the early hepatic fibrosis group,the hydroxyproline content and the level of collagen I protein in the liver in the PPAR-γtransfected group were not significantly different compared to the hepatic fibrosis group and the blank vector group;whereas the expressions of PPAR-γ andα-SMA were different compared to the hepatic fibrosis group(P<0.01).In the sustained hepatic fibrosis group,there were significant differences in the hydroxyproline content and the expression of PPAR-γ,α-SMA,and type I collagen between each group.CONCLUSION:PPAR-γcan inhibit HSC proliferation and hepatic fibrosis,and suppressα-SMA and type I collagen expression. 展开更多
关键词 peroxisome proliferator-activated receptor gamma hepatic fibrosis hepatic stellate cells lentiviral vector
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Peroxisome proliferator-activated receptor γ and colorectal cancer 被引量:5
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作者 Yun Dai Wei-Hong Wang 《World Journal of Gastrointestinal Oncology》 SCIE CAS 2010年第3期159-164,共6页
Peroxisome proliferator-activated receptors(PPARs) are members of the nuclear hormone receptor superfamily and ligand-activated transcription factors.PPARγ plays an important role in adipocyte differentiation,lipid s... Peroxisome proliferator-activated receptors(PPARs) are members of the nuclear hormone receptor superfamily and ligand-activated transcription factors.PPARγ plays an important role in adipocyte differentiation,lipid storage and energy dissipation in adipose tissue,and is involved in the control of inflammatory reactions as well as in glucose metabolism through the improvement of insulin sensitivity.Growing evidence has demonstrated that activation of PPARγ has an antineoplastic effect in tumors,including colorectal cancer.High expression of PPARγ is detected in human colon cancer cell lines and adenocarcinoma.This review describes the molecular mechanisms by which PPARγ regulates tumorigenesis in colorectal cancer,and examines current clinical trials evaluating PPARγ agonists as therapeutic agents for colorectal cancer. 展开更多
关键词 COLORECTAL cancer peroxisome proliferator-activated receptors LIGAND Tumor suppression
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Peroxisome proliferator-activated receptor-γ is essential in the pathogenesis of gastric carcinoma 被引量:13
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作者 Xiu-Mei Ma Hong Yu Na Huai 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第31期3874-3883,共10页
AIM: To investigate whether peroxisome proliferatoractivated receptor γ (PPAR-γ) is expressed in human gastric carcinoma and whether PPAR-γ, is a potential target for gastric carcinoma therapy. METHODS: PPAR-γ... AIM: To investigate whether peroxisome proliferatoractivated receptor γ (PPAR-γ) is expressed in human gastric carcinoma and whether PPAR-γ, is a potential target for gastric carcinoma therapy. METHODS: PPAR-γ protein in gastric carcinoma was examined by immunohistochemistry. In the gastric carcinoma cell line MGCS03, PPAR-7, survivin, Skp2 and p27 protein and mRNA were examined by Western blotting and real-time reverse transcription-polymerase chain reaction, respectively; proliferation was examined by MTT; apoptosis was examined by chromatin staining with Hoechst 33342 and fluorescence activated cell sorting (FACS). and cell cycle was examined by FACS; the knockdown of PPAR-γ was done by RNA interference. RESULTS: A high level of expression of PPAR-γ was observed in human gastric carcinoma and in a human gastric carcinoma cell line MGCS03. The PPAR-γ agonist 15-deoxy-△12,14-prostaglandin J2 (15d-PGJ2)inhibited growth, and induced apoptosis and G1/G0 cell cycle arrest in MGC803 cells in a concentration-dependent and time-dependent manner. The effect of 15d-PGJ2 on MGC803 cells was not reversed by the selective and irreversible antagonist GW9662 for PPAR-γ. Furthermore, survivin and Skp2 expression were decreased, whereas p27 expression was enhanced following 15d-PGJ2 treatment in a dose-dependent manner in MGC803 cells. Interestingly, we also found that small interfering RNA for PPAR-γ inhibited growth and induced apoptosis in MGC803 cells. The inhibition of PPAR-γ function may be a potentially important and novel modality for treatment and prevention of gastric carcinoma. CONCLUSION: A PPAR-γ agonist inhibited growth of human gastric carcinoma MGC803 cells by inducing apoptosis and G1/G0 cell cycle arrest with the involvement of survivin, Skp2 and p27 and not via PPAR-γ. 展开更多
关键词 peroxisome proliferator-activated receptor Gastric cancer Apoptosis Cell cycle
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Troglitazone, a peroxisome proliferator-activated receptor γ ligand, induces growth inhibition and apoptosis of HepG2 human liver cancer cells 被引量:10
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作者 Yan-Ming Zhou Yin-Hao Wen Xiao-Yan Kang Hai-Hua Qian Jia-Mei Yang Zheng-Feng Yin 《World Journal of Gastroenterology》 SCIE CAS CSCD 2008年第14期2168-2173,共6页
AIM: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS: Liver cancer cell line HepG2 was cu... AIM: To examine the effect of troglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) ligand, on the proliferation and apoptosis of human liver cancer cells. METHODS: Liver cancer cell line HepG2 was cultured and treated with troglitazone. Cell proliferation was detected by 3-(4-,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay; apoptosis was detected by flow cytometry and terminal deoxynucleotidyl transferase- mediated nick end labeling of DNA fragmentation sites (TUNEL) assay; and apoptosis-related protein was detected by immunocytochemistry and Western blotting. RESULTS: Troglitazone inhibited growth and induced apoptosis of HepG2 cells in a dose-dependent manner, and induced activation of caspase-3 expression. Troglitazone not only drove apoptosis-inhibiting factor survivin to translocate incompletely from the nucleus to the cytoplasm, but also inhibited expression of survivin, while it did not affect expression of apoptosis-promoting factor Bax. CONCLUSION: PPARγ ligands inhibit growth and induce apoptosis of liver cancer cells, and may have applications for the prevention and treatment of liver cancer. 展开更多
关键词 peroxisome proliferator-activated receptor γ TROGLITAZONE Liver neoplasms APOPTOSIS
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Suppression of pancreatic carcinoma growth by activating peroxisome proliferator-activated receptor γ involves angiogenesis inhibition 被引量:13
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作者 Yu-Wei Dong Xing-Peng Wang Kai Wu 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第4期441-448,共8页
AIM: TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METH... AIM: TO Study the possible actions and mechanisms or peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor, in pancreatic car- cinogenesis, especially in angiogenesis. METHODS: Expressions of PPARy and retinoid acid receptor (RXRα) were examined by reverse-transcription polymerase chain reaction (RT-PCR) with immunocyto- chemical staining. Pancreatic carcinoma cells, PANC-1, were treated either with 9-cis-RA, a ligand of RXRα, or with 15-deoxy-△12,14 prostaglandin J2 (15d-PGJ2), a ligand of PPART, or both. Antiproliferative effect was evaluated by cell viability using methyltetrazolium (MTT) assay. A pancreatic carcinoma xenograft tumor model of nude mice was established by inoculating PANC-1 cells subcutaneously. Rosiglitazone, a specific ligand of PPARy, was administered via water drinking in experimental group of nude mice. After 75 d, all mice were sacrificed. Expression of proliferating cell nuclear antigen (PCNA) in tumor tissue was examined with immunohistochemical staining. Expression of vascular endothelial growth factor (VEGF) mRNA in PANC-1 cells, which were treated with 15d-PGJ2 or 9-cis-RA at various concentrations or different duration, was detected by semi-quantitative RT-PCR. Effects of Rosi- glitazone on changes of microvascular density (MVD) and VEGF expression were investigated in xenograft tumor tissue. Neovasculature was detected with immu- nohistochemistry staining labeled with anti-Ⅳ collagen antibody, and indicated by MVD. RESULTS: RT-PCR and immunocytochemical stain- ing showed that PPARγ and RXRα were expressed in PANC-1 cells at both transcription level and translation level. MTT assay demonstrated that 15d-PGJ2, 9-cis-RA and their combination inhibited the growth of PANC-1 cells in a dose-dependent manner. 9-cis-RA had a com- bined inhibiting action with 15d-PGJ2 on the growth of pancreatic carcinoma. In vivo studies revealed that Rosiglitazone significantly suppressed the growth of pancreatic carcinoma as compared to control group (0.48 ± 0.23 cm^3 vs 2.488 ± 0.59 cm^3, P 〈 0.05), and the growth inhibition rate was 80.7%. Immuno- histochemistry study showed that PCNA was down regulated in Rosiglitazone-treated group compared to the control group. 15d-PGJ2, 9-cis-RA and their com- bination inhibited the expression of VEGF mRNA in PANC-1 cells in a dose- and time-dependent manner. MVD was decreased more significantly in Rosiglitazone- treated mice (10.67±3.07) than in the control group (31.44±6.06) (P 〈 0.01). VEGF expression in xeno- graft tumor tissue was also markedly down-regulated in Rosiglitazone-treated mice. CONCLUSION: Activation of PPARγ, inhibits the growth of pancreatic carcinoma both in vitro and in vivo. Sup- pression of tumor angiogenesis by down-regulating the expression of VEGF may be one of the mechanisms by which PPARγ, activation inhibits the growth of pancre- atic carcinoma. 展开更多
关键词 Pancreatic carcinoma peroxisome prolifer-ator-activated receptor γ ANGIOGENESIS Vascular en-dothelial growth factor
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