Association between the Pro12Ala polymorphism of PPAR-γ gene and the non-alcoholic fatty liver disease: A meta-analysis

Wang, Jun; Guo, Xufeng; Wu, Pengbo; Song, Jia; Ye, Chuncui; Yu, Shijie; Zhang, Jixiang; Dong, Weiguo

doi:10.1016/j.gene.2013.07.014

Cited by 16 publications

(14 citation statements)

References 32 publications

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“…PPARγ increases the expression of lipoprotein lipase, which is an enzyme that serves to partition fat to adipocytes, limiting fatty acid flux to the liver [36] . In this study, compared to the model group, the expression of PPARγ was significantly down-regulated in the GP treatment groups, which indicated that the protective mechanism of the GPs may be related to PPARγ.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

et al. 2015

WJG

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AIM:To explore the mechanism of action of gypenosides (GPs) on type 2 diabetes mellitus and non-alcoholic fatty liver disease (T2DM-NAFLD) in rats. METHODS:Sixty rats were randomly divided into a healthy group, an untreated disease model group and GP-treatment groups. The study involved the evaluation of biochemical parameters, including serum aspartate transaminase (AST), alanine transferase (ALT), blood glucose (BG), triglycerides (TG) and total cholesterol (TC). Additionally, the protective effect of the treatments were confirmed histopathologically and the expression of TNF-α and NF-κB in the rat liver was analyzed using immunohistochemistry. The expression of proliferatoractivated receptor gamma (PPARγ) and cytochrome P450 (CYP450) 1A1 mRNA was determined by quantitative RT-PCR. RESULTS:GP treatments at oral doses of 200, 400, and 800 mg/kg per day significantly decreased the levels of serum AST and ALT (P < 0.05, P < 0.01), especially at the dose of 800 mg/kg per day. To a similar extent, GP at 800 mg/kg per day reduced the levels of BG (4.19 ± 0.47, P < 0.01), TG (80.08 ± 10.05, P < 0.01), TC (134.38 ± 16.39, P < 0.01) and serum insulin (42.01 ± 5.04, P < 0.01). The expression of TNF-α and NF-κB measured by immunohistochemistry was significantly reduced by GPs in a dose-dependent manner, and the expression of PPARγ and CYP4501A1 mRNA, as measured using quantitative real-time PCR, were significantly down-regulated by GPs. Moreover, GPs decreased the infiltration of liver fats and reversed the histopathological changes in a dosedependent manner. CONCLUSION:This study suggests that GPs have a protective effect against T2DM-NAFLD by down-regulating the expression of TNF-α and NF-κB proteins, and PPARγ and CYP4501A1 mRNAs. Core tip: Gypenosides (GPs) are one of the most pharmacologically active components in G. pentaphyllum . Basic Study ORIGINAL ARTICLEHe Q et al . Mechanism of action of GPs on T2DM-NAFLD Intervention with GPs significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase, blood glucose, insulin, triglycerides and total cholesterol in type 2 diabetes mellitus and non-alcoholic fatty liver disease (T2DM-NAFLD) model rats, down-regulated the expression of TNF-α, NF-κB, rabbit anti-proliferator activated receptory (PPARγ) and rabbit anti-cytochrome P4501A1 (CYP1A1) mRNA, decreased the infiltration of liver fats and reversed the histopathological changes in a dose-dependent manner. These findings suggest that GPs have a protective effect against T2DM-NAFLD by downregulating the expression of TNF-α and NF-κB proteins, and PPARγ and CYP4501A1 mRNAs.He Q, Li JK, Li F, Li RG, Zhan GQ, Li G, Du WX, Tan HB. Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats.

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Section: Discussionmentioning

confidence: 99%

Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

et al. 2015

WJG

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“…Similarly, a Pro12Ala SNP has been documented for PPAR-γ. Though earlier studies have documented many NAFLD patients with the alanine variant of PPAR-γ, recent meta-analyses have failed to establish such an association between Pro12Ala SNP and NAFLD risk [50] . Further investigations are required to corroborate such findings.…”

Section: Role Of Ppars In Nafldmentioning

confidence: 98%

“…Endogenous ligands of PPARs include FFA and eicosanoids [49] . Activation of PPAR-γ can promote secretion of antihyperglycemic adipokines like adiponectin, and shift the deposition of non-esterified fatty acids (NEFAs) to adipose tissue and away from liver and skeletal muscle, as it serves as an activator of lipoprotein lipase [50] . Moreover, adiponectin can increase PPAR-γ in adipose tissue.…”

Section: Function Of Peroxisome Proliferator-activated Receptors In Lmentioning

confidence: 99%

Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease

Giby

Ajith

2014

WJH

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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. Evidence 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 lipogenesis, 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, transforming 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 factors, namely peroxisome proliferator-activated receptor (PPAR)-α. Recent studies have proposed downregulation of PPAR-α in cases of hepatic steatosis. This review discusses the role of adipokines and PPARs with regard to hepatic energy metabolism and progression of NAFLD.

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“…For example, an increased expression of cytochrome P450-2E1 has been found in patients with NAFLD [64,65] and polymorphisms in peroxisome proliferator-activated receptors (PPAR) alpha and gamma2 have been suggested to be linked to the risk of NAFLD [66].…”

Section: Future Research Perspectivesmentioning

confidence: 99%

The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease

Pastori¹,

Polimeni²,

Baratta³

et al. 2015

Digestive and Liver Disease

135

104

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Non-alcoholic fatty liver disease is an emerging liver disease in Western countries and the most frequent cause of incidental elevation of serum liver enzymes. Dyslipidaemia is frequently observed in patients with non-alcoholic fatty liver disease, and treatment of dyslipidaemia plays a critical role in the overall management of these patients. Moreover, coronary artery disease remains the most common cause of death. Statins are effective lipid-lowering agents, associated with a lowering the risk of cardiovascular events in several interventional randomized clinical trials. However, statins are often underused in patients with non-alcoholic fatty liver disease and many physicians are concerned about the prescription of statins to patients with unexplained persistent elevation of liver enzymes or active liver disease. Based on currently available data, statin therapy, at low-to-moderate doses, seems to be safe and has low liver toxicity. Treatment of dyslipidaemia in patients with non-alcoholic fatty liver disease is recommended and may also improve liver function tests. In these patients, the risks of not taking statins could outweigh the risks of taking the drug. Conversely, the usefulness of statins for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis is still a matter of debate and randomized clinical trials of adequate size and duration are required.

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Association between the Pro12Ala polymorphism of PPAR-γ gene and the non-alcoholic fatty liver disease: A meta-analysis

Cited by 16 publications

References 32 publications

Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats

Role of adipokines and peroxisome proliferator-activated receptors in nonalcoholic fatty liver disease

The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease

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