Natural PPARs agonists for the treatment of nonalcoholic fatty liver disease

Pan, Jiashu; Zhou, Wenjun; Xu, Ru; Xing, Lian-Jun; Ji, Guang; Dang, Yanqi

doi:10.1016/j.biopha.2022.113127

Cited by 19 publications

(14 citation statements)

References 108 publications

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“…Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcriptional factors, which belong to the nuclear receptor superfamily and play key roles in lipid and glucose metabolism [1][2][3][4]. Humans have three subtypes of PPARs: PPARα, PPARδ (also named as PPARβ), and PPARγ.…”

Section: Introductionmentioning

confidence: 99%

C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis

Zhang

et al. 2023

Horm Metab Res

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The relationships of the PPARα Leu162Val and PPARδ+294 T>C polymorphisms with metabolic indexes have been reported to be inconsistent and even contradictory. The meta-analysis was conducted to clarify the relationships between the two variants and the indexes of obesity, insulin resistance, and blood lipids. PubMed, Google Scholar, Embase, and Cochrane Library were searched for eligible studies. Standardized mean difference with 95% confidence interval was calculated to estimate the differences in the metabolic indexes between the genotypes of the Leu162Val and+294 T>C polymorphisms. Heterogeneity among studies was assessed by Cochran’s x2-based Q-statistic test. Publication bias was identified by using Begg’s test. Forty-one studies (44 585 subjects) and 33 studies (23 018 subjects) were identified in the analyses for the Leu162Val and+294 T>C polymorphisms, respectively. C allele carriers of the+294 T>C polymorphism had significantly higher levels of total cholesterol and low-density lipoprotein cholesterol than TT homozygotes in the whole population. Notably, C allele carriers of the+294 T>C polymorphism had significantly higher levels of triglycerides and total cholesterol in East Asians, but lower levels of triglycerides in West Asians than TT homozygotes. Regarding the Leu162Val polymorphism, it was found that Val allele carriers had significantly higher levels of blood glucose than Leu/Leu homozygotes only in European Caucasians. The meta-analysis demonstrates that C allele of the+294 T>C polymorphism in PPARδ gene confers a higher risk of hypercholesterolemia, which may partly explain the relationship between this variant and coronary artery disease.

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Section: Introductionmentioning

confidence: 99%

C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis

Zhang

et al. 2023

Horm Metab Res

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“…This phenomenon is analogous to the ‘two-hit’ hypothesis that is observed in other conditions with renal manifestations such as autosomal dominant polycystic kidney disease (ADPKD) (11), tuberous sclerosis (12) and von Hippel-Lindau disease (13). Recent work also demonstrates that non-alcoholic fatty liver disease (NAFLD), the risk of which is heightened by the presence of type 2 diabetes, is characterized by a ‘two-hit’ or even a ‘multi-hit’ hypothesis which also includes a hyperinflammatory state and dysregulated Wnt signaling in addition to triglyceride accumulation in hepatocytes (14).…”

Section: Discussionmentioning

confidence: 99%

Loss of endothelial glucocorticoid receptor accelerates organ fibrosis indb/dbmice

Srivastava

Goodwin

2023

Preprint

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Endothelial cells play a key role in maintaining homeostasis and are deranged in many disease processes, including fibrotic conditions. Absence of the endothelial glucocorticoid receptor (GR) has been shown to accelerate diabetic kidney fibrosis in part through up regulation of Wnt signaling. The db/db mouse model is a model of spontaneous type 2 diabetes that has been noted to develop fibrosis in multiple organs over time, including the kidneys. This study aimed to determine the effect of loss of endothelial GR on organ fibrosis in the db/db model. Db/Db mice lacking endothelial GR showed more severe fibrosis in multiple organs compared to endothelial GR-replete db/db mice. Organ fibrosis could be substantially improved either through administration of a Wnt inhibitor or metformin. IL-6 is a key cytokine driving the fibrosis phenotype and is mechanistically linked to Wnt signaling. The db/db model is an important tool to study mechanisms of fibrosis and its phenotype in the absence of endothelial GR highlights the synergistic effects of Wnt signaling and inflammation in the pathogenesis or organ fibrosis.

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“…The lipolysis of white adipose tissue results in increased FFA levels and enhanced TAG synthesis in the liver. Among the several factors involved in adipose tissue regulation, PPARγ is considered the "master regulator" of adipogenesis [55,56]. The PPARγ is a well-characterized regulator of energy metabolism mainly by improving uptake and expenditure of fatty acid in adipocyte and is clearly involved in the pathophysiology of obesity and related complications.…”

Section: Pparα and Pparγ Functions In Adipose Tissuementioning

confidence: 99%

Roles of PPARα and PPARγ As Regulator of Free Fatty Acids in Nonalcoholic Steatohepatitis

Vu¹,

Nguyen²,

Matsubara³

2023

Preprint

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In recent years, nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) has become a leading worldwide disease, and its therapies are facing many complexities. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the nuclear receptor (NR) superfamily and have three subtypes: PPARα (NR1C1), PPARβ/δ (NR1C2), and PPARγ (NR1C3). They have been identified to be essential in the regulation of lipid metabolism by controlling the transcription of genes related to fatty acids, bile acids, and cholesterol metabolism. Many PPAR agonists have been reported, such as natural agonists (fatty acids, eicosanoids, and phospholipids) and synthetic ligands (fibrates, thiazolidinediones, glitazars, and elafibranor). PPAR-based chemicals have a breakthrough in the innovation of therapy for fatty liver disease. This review will provide an overview of how PPARα and PPARγ play roles in lipid homeostasis, discussing the consideration of their agonists as potential therapeutic agents for NAFLD/NASH.

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Natural PPARs agonists for the treatment of nonalcoholic fatty liver disease

Cited by 19 publications

References 108 publications

C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis

C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis

Loss of endothelial glucocorticoid receptor accelerates organ fibrosis indb/dbmice

Roles of PPARα and PPARγ As Regulator of Free Fatty Acids in Nonalcoholic Steatohepatitis

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