scholarly journals Paradoxical Protective Effect of Perfluorooctanesulfonic Acid Against High-Fat Diet–Induced Hepatic Steatosis in Mice

2018 ◽  
Vol 37 (5) ◽  
pp. 383-392 ◽  
Author(s):  
Ian Huck ◽  
Kevin Beggs ◽  
Udayan Apte
Keyword(s):  
Hepatic Steatosis ◽  
Lipid Content ◽  
High Fat Diet ◽  
Organic Pollutant ◽  
Dietary Lipid ◽  
Chow Diet ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Perfluorooctanesulfonic Acid

Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant with worldwide bioaccumulation due to a very long half-life. Perfluorooctanesulfonic acid exposure results in significant hepatic effects including steatosis, proliferation, hepatomegaly, and in rodents, carcinogenesis. The objective of this study was to determine whether PFOS exposure exacerbates nonalcoholic fatty liver disease and nonalcoholic steatohepatitis pathogenesis. Eight-week-old male C57BL/6 J mice (n = 5 per group) were fed ad libitum normal chow diet (ND) alone, 60% high-fat diet (HFD) alone, ND + PFOS, and HFD + PFOS (0.0001% w/w (1 mg/kg) of PFOS) for 6 weeks. Both HFD alone and the ND + PFOS treatment induced significant adiposity and hepatomegaly, but the HFD + PFOS treatment showed a marked protection. Oil Red O staining and quantitative analysis of hepatic lipid content revealed increased hepatic steatosis in ND + PFOS and in HFD alone fed mice, which was prevented in HFD + PFOS treatment. Further studies revealed that ND + PFOS treatment significantly affected expression of lipid trafficking genes to favor steatosis, but these changes were absent in HFD + PFOS group. Specifically, expression of CD36, the major lipid importer in the cells, and peroxisome proliferator-activated receptor gamma (PPARγ), its major regulator, were induced in HFD + no treatment (NT) and ND + PFOS-fed mice but remained unchanged in HFD + PFOS mice. In conclusion, these data indicate that coadministration of PFOS with HFD mitigates steatosis and hepatomegaly induced by HFD and that by PFOS fed in ND diet via regulation of cellular lipid import machinery. These findings suggest dietary lipid content be considered when performing risk management of PFOS in humans and the elucidation of PFOS-induced hepatotoxicity.

scholarly journals PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR-γ/CD36 Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Yu Liu ◽  
Fei Cheng ◽  
Yuxuan Luo ◽  
Zhu Zhan ◽  
Peng Hu ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Lipid ◽  
Serum Triglyceride ◽  
The Body ◽  
Chow Diet ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Curcumin Derivative

Curcumin has the potential to cure dyslipidemia and nonalcoholic fatty liver disease (NAFLD). However, its therapeutic effects are curbed by poor bioavailability. Our previous work has shown that modification of curcumin with polyethylene glycol (PEG) improves blood concentration and tissue distribution. This study sought to investigate the role of a novel PEGylated curcumin derivative (Curc-mPEG454) in regulating hepatic lipid metabolism and to elucidate the underlying molecular mechanism in a high-fat-diet- (HFD-) fed C57BL/6J mouse model. Mice were fed either a control chow diet (D12450B), an HFD (D12492) as the NAFLD model, or an HFD with Curc-mPEG454 administered by intraperitoneal injection at 50 mg/kg or 100 mg/kg for 16 weeks. We found that Curc-mPEG454 significantly lowered the body weight and serum triglyceride (TG) levels and reduced liver lipid accumulation in HFD-induced NAFLD mice. It was also shown that Curc-mPEG454 suppressed the HFD-induced upregulated expression of CD36 and hepatic peroxisome proliferator activated receptor-γ (PPAR-γ), a positive regulator of CD36. Moreover, Curc-mPEG454 dramatically activated cAMP response element-binding (CREB) protein, which negatively controls hepatic PPAR-γ expression. These findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.

scholarly journals Protective Effect of a Mixture of Astragalus membranaceus and Lithospermum erythrorhizon Extract against Hepatic Steatosis in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Doo Jin Choi ◽  
Seong Cheol Kim ◽  
Gi Eun Park ◽  
Bo-Ram Choi ◽  
Dae Young Lee ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Density Lipoprotein ◽  
Lithospermum Erythrorhizon ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

The present study aimed to evaluate the potential synergistic and protective effects of ALM16, a mixture of Astragalus membranaceus (AM) and Lithospermum erythrorhizon (LE) extract in a ratio of 7 : 3, against hepatic steatosis in high fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) mice. Forty-eight mice were randomly divided into eight groups and orally administered daily for 6 weeks with a normal diet (ND) or high fat diet alone (HFD), HFD with AM (HFD + 100 mg/kg AM extract), HFD with LE (HFD + 100 mg/kg LE extract), HFD with ALM16 (HFD + 50, 100, and 200 mg/kg ALM16), or HFD with MT (HFD + 100 mg/kg Milk thistle extract) as a positive control. ALM16 significantly decreased the body and liver weight, serum and hepatic lipid profiles, including triglyceride (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL), and low-density lipoprotein-cholesterol (LDL), and serum glucose levels, compared to the HFD group. Moreover, ALM16 significantly ameliorated the HFD-induced increased hepatic injury markers, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma-glutamyltransferase (GGT)-1. Furthermore, as compared to the mice fed HFD alone, ALM16 increased the levels of phosphorylated AMP-activated protein kinase (p-AMPK) and acetyl-CoA carboxylase (p-ACC), thereby upregulating the expression of carnitine palmitoyltransferase (CPT)-1 and downregulating the expression of sterol regulatory element-binding protein (SREBP)-1c and fatty acid synthase (FAS). These results demonstrated that ALM16 markedly inhibited HFD-induced hepatic steatosis in NAFLD mice by modulating AMPK and ACC signaling pathways, and may be more effective than the single extracts of AM or LE.

scholarly journals Sijunzi, Lizhong, and Fuzilizhong Decoction Alleviate Nonalcoholic Fatty Liver Disease through Activation of PPAR Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Jiayao Yang ◽  
Dongqing Tao ◽  
Wei Ma ◽  
Song Liu ◽  
Yan Liao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Peroxisome Proliferator ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Chinese Herbal

Objective. Sijunzi, Lizhong, and Fuzilizhong decoction were traditional Chinese classic formulations, which are widely used in clinical treatment, and the underlying mechanism is unclear. In this study, we aim to investigate the molecular mechanisms underlying the protective effects of Sijunzi, Lizhong, and Fuzilizhong on nonalcoholic fatty liver disease (NAFLD). Methods. Male Wistar rats were fed a high-fat diet for four weeks to induce NAFLD and were thereafter administered Sijunzi (8 g/kg/d), Lizhong (10 g/kg/d), or Fuzilizhong (10 g/kg/d) by gavage for four weeks. Hepatic damage, lipid accumulation, inflammation, autophagy, and peroxisome proliferator-activated receptor-α signaling were evaluated. Results. The high-fat diet-fed rats showed typical symptoms of NAFLD, including elevated levels of hepatic damage indicators, increased hepatic lipid deposition and fibrosis, severe liver inflammation, and prominent autophagy. Upon administration of Sijunzi, Lizhong, and Fuzilizhong, liver health was improved remarkably, along with ameliorated symptoms of NAFLD. In addition, NAFLD-suppressed peroxisome proliferator-activated receptor-α signaling was reactivated after treatment with the three types of decoctions. Conclusions. The results collectively signify the effective therapeutic and protective functions of Sijunzi, Lizhong, and Fuzilizhong against NAFLD and demonstrate the potential of Chinese herbal medication in mitigating the symptoms of liver diseases. Novelty of the Work. Traditional Chinese herbal medicine has been used for centuries to treat various diseases, but the molecular mechanisms of individual ingredients have rarely been studied. The novelty of our work lies in elucidating the specific signaling pathways involved in the control of NAFLD using three common Chinese herbal decoctions. We suggest that natural herbal formulations can be effective therapeutic agents to combat against NAFLD.

scholarly journals Ginsenoside Rb1 Alleviated High-Fat-Diet-Induced Hepatocytic Apoptosis via Peroxisome Proliferator-Activated Receptor γ

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bing Song ◽  
Yao Sun ◽  
Yafen Chu ◽  
Jing Wang ◽  
Hongwei Zheng ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
High Fat Diet ◽  
Hepatic Cell ◽  
Peroxisome Proliferator ◽  
Ginsenoside Rb1 ◽  
Hepatocyte Apoptosis ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Induced Apoptosis

Objective. High-fat-diet- (HFD-) induced hepatic cell apoptosis is common in mice with nonalcoholic fatty liver disease (NAFLD). We aim to investigate the effect of Ginsenoside Rb1 (GRb1) on hepatocyte apoptosis. Methods. C57BL/6J mice with HFD were used to induce a liver-injured model with cell apoptosis. In addition, GRb1 was used to treat HFD-induced apoptosis in a liver with or without inhibitor of peroxisome proliferator-activated receptor γ (PPAR-γ). Results. Compared with C57BL/6J mice with common chow, there are downregulated PPAR-γ but upregulated cell apoptosis in the liver of mice with HFD. Furthermore, GRb1 elevated the hepatic PPAR-γ level and suppressed hepatocytic apoptosis. However, GW9662 abolished the effects of GRb1 on apoptosis in the liver. Conclusions. GRb1 alleviated HFD-induced apoptosis of hepatocytes of mice via PPAR-γ.

scholarly journals The kielin/chordin-like protein KCP attenuates nonalcoholic fatty liver disease in mice

2016 ◽  
Vol 311 (4) ◽  
pp. G587-G598 ◽  
Author(s):  
Abdul Soofi ◽  
Katherine I. Wolf ◽  
Egon J. Ranghini ◽  
Mohammad A. Amin ◽  
Gregory R. Dressler
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Liver Pathology ◽  
Wild Type ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and is increasing with the rising rate of obesity in the developed world. Signaling pathways known to influence the rate of lipid deposition in liver, known as hepatic steatosis, include the transforming growth factor (TGF) superfamily, which function through the SMAD second messengers. The kielin/chordin-like protein (KCP) is a large secreted protein that can enhance bone morphogenetic protein signaling while suppressing TGF-β signaling in cells and in genetically modified mice. In this report, we show that aging KCP mutant ( Kcp −/−) mice are increasingly susceptible to developing hepatic steatosis and liver fibrosis. When young mice are put on a high-fat diet, Kcp −/− mice are also more susceptible to developing liver pathology, compared with their wild-type littermates. Furthermore, mice that express a Pepck-KCP transgene ( Kcp Tg) in the liver are resistant to developing liver pathology even when fed a high-fat diet. Analyses of liver tissues reveal a significant reduction of P-Smad3, consistent with a role for KCP in suppressing TGF-β signaling. Transcriptome analyses show that livers from Kcp −/− mice fed a normal diet are more like wild-type livers from mice fed a high-fat diet. However, the KCP transgene can suppress many of the changes in liver gene expression that are due to a high-fat diet. These data demonstrate that shifting the TGF-β signaling paradigm with the secreted regulatory protein KCP can significantly alter the liver pathology in aging mice and in diet-induced NAFLD.

scholarly journals Bixin Attenuates High-Fat Diet-Caused Liver Steatosis and Inflammatory Injury through Nrf2/PPARα Signals

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Shasha Tao ◽  
Youjing Yang ◽  
Jianzhong Li ◽  
Hongyan Wang ◽  
Yu Ma
Keyword(s):  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Cytoprotective Activity ◽  
Inflammatory Damage

Nonalcoholic fatty liver disease is the most common liver disease worldwide. Hepatic steatosis and oxidative stress are the main characteristics of NAFLD (nonalcoholic fatty liver disease), which also affect its prognosis. Bixin acts as novel Nrf2 (NF-E2 p45-related factor 2) activator with the cytoprotection against oxidative stress and inflammation; this study mainly focused on the mechanism of Nrf2 activation by bixin and explored its potential feasibilities in long-term high-fat diet- (HFD-) caused hepatic steatosis and inflammatory response in vitro and in vivo. Bixin was found to activate Nrf2 signals by the modification of critical Keap1 (Kelch-like ECH-associated protein 1) cystine and competitive interaction with Keap1 with upregulating P62 mRNA and protein expression. In human liver cells exposed to FFA (free fatty acid), bixin displayed a pronounced cytoprotective activity with upregulation of Nrf2-mediated gene expression, such as PPARα and its targets related with fatty acid oxidation. In HFD-fed mice, systemic administration of bixin attenuated lipid accumulation, decreased oxidant inflammatory damage in the liver, and reduced circulating lipid levels through Nrf2. Different from most of other established inducers, bixin activated Nrf2 signals through two different mechanisms with safe administration for protection of oxidant inflammatory damage and attenuation of lipid accumulation in the in vivo long-term HFD-fed mice. Bixin represents a prototype Nrf2 activator that displays cytoprotective activity upon system administration targeting hepatic steatosis and oxidant inflammation originating from long-term HFD-fed mice. And bixin-based Nrf2-directed systemic intervention may also provide therapeutic benefit in protecting other organs in the process of metabolic syndrome.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Ningjing Zhang ◽  
Junxian Tao ◽  
Lijun Gao ◽  
Yan Bi ◽  
Ping Li ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gut Microbiota ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Fatty Liver Disease ◽  
Structural Changes ◽  
High Fat ◽  
Nonalcoholic Fatty Liver

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.

The effect of various high-fat diet on liver histology in the development of NAFLD models in mice

2021 ◽  
Vol 32 (4) ◽  
pp. 547-553
Author(s):  
Mahardian Rahmadi ◽  
Ahmad Dzulfikri Nurhan ◽  
Eka Dewi Pratiwi ◽  
Devita Ardina Prameswari ◽  
Sisca Melani Panggono ◽  
...  
Keyword(s):  
Beef Tallow ◽  
High Fat Diet ◽  
Corn Oil ◽  
Model Development ◽  
Liver Histology ◽  
Control Group ◽  
Chow Diet ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
The World

Abstract Objectives Nonalcoholic fatty liver disease (NAFLD) is exceptionally common around the world. The development of NAFLD is increasing rapidly in the world, along with changes in lifestyle. Excess lipid intake is one of the risk factors for NAFLD. The NAFLD model is induced by a high-fat diet contains SFA, MUFA, and ῳ-6 PUFA. This study aims to assess the effect of high-fat diet variation on liver histology in developing NAFLD models in mice. Methods Thirty-six male mice (Balb/c) were divided into six groups fed a high-fat diet containing beef tallow 60%, beef tallow 45%, vegetable ghee, animal ghee + corn oil, vegetable ghee + corn oil for 28 days and compared to a control group fed a chow diet. All of the mice were fed with a high-fat diet in the form of pellets ad libitum for 28 days. Bodyweight and food intake were measured every day. At the last day of treatment, animals were sacrificed and the Liver were taken for histological analysis. Results This study showed that NAFLD model development was achieved in all group mice fed a high-fat diet with different degrees of NAFLD. Beef tallow 60% had the worst liver histology. Conclusions Thus, based on this study, we found that high-fat diet variations influenced the development of NAFLD models in mice, particularly concerning liver histology.

scholarly journals Vildagliptin Can Alleviate Endoplasmic Reticulum Stress in the Liver Induced by a High Fat Diet

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaoqing Ma ◽  
Wenhua Du ◽  
Shanshan Shao ◽  
Chunxiao Yu ◽  
Lingyan Zhou ◽  
...  
Keyword(s):  
Er Stress ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
Liver Weight ◽  
Chow Diet ◽  
High Fat ◽  
Western Blots ◽  
Nonalcoholic Fatty Liver ◽  
Expression Levels

Purpose. We investigated whether a DDP-4 inhibitor, vildagliptin, alleviated ER stress induced by a high fat diet and improved hepatic lipid deposition. Methods. C57BL/6 mice received standard chow diet (CD), high fat diet (HFD), and HFD administered with vildagliptin (50 mg/Kg) (V-HFD). After administration for 12 weeks, serum alanine aminotransferase, glucose, cholesterol, triglyceride, and insulin levels were analyzed. Samples of liver underwent histological examination and transmission electron microscopy, real-time PCR for gene expression levels, and western blots for protein expression levels. ER stress was induced in HepG2 cells with palmitic acid and the effects of vildagliptin were investigated. Results. HFD mice showed increased liver weight/body weight (20.27%) and liver triglycerides (314.75%) compared to CD mice, but these decreased by 9.27% and 21.83%, respectively, in V-HFD mice. In the liver, HFD induced the expression of ER stress indicators significantly, which were obviously decreased by vildagliptin. In vitro, the expressions of molecular indicators of ER stress were reduced in HepG2 when vildagliptin was administered. Conclusions. Vildagliptin alleviates hepatic ER stress in a mouse high fat diet model. In HepG2 cells, vildagliptin directly reduced ER stress. Therefore, vildagliptin may be a potential agent for nonalcoholic fatty liver disease.

Rhus verniciflua and Eucommia ulmoides Protects Against High-Fat Diet-Induced Hepatic Steatosis by Enhancing Anti-Oxidation and AMPK Activation

2019 ◽  
Vol 47 (06) ◽  
pp. 1253-1270
Author(s):  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Young Yoon ◽  
Han-Jung Chae
Keyword(s):  
Protein Folding ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Disorder ◽  
Eucommia Ulmoides ◽  
High Fat ◽  
Nonalcoholic Fatty Liver ◽  
Rhus Verniciflua ◽  
Anti Oxidant

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder associated with features of metabolic syndrome and oxidative stress. We examined the mechanism by which the combined extracts of Rhus verniciflua and Eucommia ulmoides extracts (ILF-RE) regulate hepatic dyslipidemia in an established NAFLD model, high-fat diet (HFD)-induced lipid dysmetabolism in rats. ILF-RE attenuated alanine aminotransferase (ALT) by 1.5% [Formula: see text], aspartate aminotransferase (AST) by 1.5% [Formula: see text], triglycerides by 1.5% [Formula: see text], cholesterol by 2.0% [Formula: see text], and lipid peroxidation by 1.5% [Formula: see text] in the NAFLD model. ILF-RE, recently shown to have anti-oxidant properties, also inhibited hepatic ROS accumulation by 1.68% [Formula: see text] and regulated ER-redox imbalance, a key phenomenon of ER stress. Due to nutrient overload stress-associated protein folding, ER stress and downstream SREBP-lipogenic transcription signaling were highly activated, and the mTORC1-AMPK axis was also disturbed, leading to hepatic steatosis. ILF-RE results in recovery from hepatic conditions induced by nutrient-based protein folding stress signaling and the ER stress-SREBP and AMPK-mTORC1-SREBP1 axes. Based on these results, ILF-RE is suggested to be a potential therapeutic strategy for hepatic steatosis and may represent a promising novel agent for the prevention and treatment of NAFLD.

Sign in / Sign up

Export Citation Format

Share Document