Resveratrol Ameliorates Alcoholic Fatty Liver by Inducing Autophagy

2016 ◽  
Vol 44 (06) ◽  
pp. 1207-1220 ◽  
Author(s):  
Liying Tang ◽  
Fengli Yang ◽  
Zhirui Fang ◽  
Chengmu Hu
Keyword(s):  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Early Stage ◽  
Low Density Lipoprotein ◽  
Specific Inhibitor ◽  
Density Lipoprotein ◽  
Protective Effects ◽  
Alcoholic Fatty Liver

Alcoholic fatty liver (AFL) is early stage of alcoholic liver disease, which can progress to steatohepatitis, fibrosis, and cirrhosis if alcohol consumption is continued. The pathogenesis of AFL is associated with excessive lipid accumulation in hepatocytes. Resveratrol (RES), a dietary polyphenol found in red wines and grapes, has been shown to have a hepatoprotective effect. Autophagy is a crucial physiological process in cellular catabolism that involves the regulation of lipid droplets. Autophagy maintains a balance between protein synthesis, degradation and self-recycling. In the present study, we evaluated the protective effects of RES (10[Formula: see text]mg/kg, 30[Formula: see text]mg/kg, 100[Formula: see text]mg/kg) on AFL mice fed with an ethanol Lieber-DeCarli liquid diet, and HepG2 cells in the presence of oleic acid and alcohol to investigate whether resveratrol could induce autophagy to attenuate lipid accumulation. The results showed that RES (30[Formula: see text]mg/kg and 100[Formula: see text]mg/kg) treatment significantly attenuated hepatic steatosis and lowered the activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), low density lipoprotein cholesterol (LDL-C). H&E staining showed that RES reduced hepatic lipid accumulation. Transmission electron microscopy (TEM) images showed that RES treatment increased the number of autophagosomes and promoted the formation of autophagy. Western blot analysis showed that RES treatment increased the levels of microtubule-associated protein light chain3- II (LC3-II) and Beclin1, decreased expression of p62 protein. In addition, in vitro studies also demonstrated that RES led to the formation of acidic vesicular organelles (AVOs), however, 3-Methyladenine (3-MA), a specific inhibitor of autophagy, obviously inhibited the above effects of RES. In conclusion, RES has protective effects on alcoholic hepatic steatosis, and the potential mechanism might be involved in inducing autophagy.

scholarly journals miRNA-132 induces hepatic steatosis and hyperlipidaemia by synergistic multitarget suppression

Gut ◽  
2017 ◽  
Vol 67 (6) ◽  
pp. 1124-1134 ◽  
Author(s):  
Geula Hanin ◽  
Nadav Yayon ◽  
Yonat Tzur ◽  
Rotem Haviv ◽  
Estelle R Bennett ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Mouse Models ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Obese Mice ◽  
Alcoholic Fatty Liver

ObjectiveBoth non-alcoholic fatty liver disease (NAFLD) and the multitarget complexity of microRNA (miR) suppression have recently raised much interest, but the in vivo impact and context-dependence of hepatic miR-target interactions are incompletely understood. Assessing the relative in vivo contributions of specific targets to miR-mediated phenotypes is pivotal for investigating metabolic processes.DesignWe quantified fatty liver parameters and the levels of miR-132 and its targets in novel transgenic mice overexpressing miR-132, in liver tissues from patients with NAFLD, and in diverse mouse models of hepatic steatosis. We tested the causal nature of miR-132 excess in these phenotypes by injecting diet-induced obese mice with antisense oligonucleotide suppressors of miR-132 or its target genes, and measured changes in metabolic parameters and transcripts.ResultsTransgenic mice overexpressing miR-132 showed a severe fatty liver phenotype and increased body weight, serum low-density lipoprotein/very low-density lipoprotein (LDL/VLDL) and liver triglycerides, accompanied by decreases in validated miR-132 targets and increases in lipogenesis and lipid accumulation-related transcripts. Likewise, liver samples from both patients with NAFLD and mouse models of hepatic steatosis or non-alcoholic steatohepatitis (NASH) displayed dramatic increases in miR-132 and varying decreases in miR-132 targets compared with controls. Furthermore, injecting diet-induced obese mice with anti-miR-132 oligonucleotides, but not suppressing its individual targets, reversed the hepatic miR-132 excess and hyperlipidemic phenotype.ConclusionsOur findings identify miR-132 as a key regulator of hepatic lipid homeostasis, functioning in a context-dependent fashion via suppression of multiple targets and with cumulative synergistic effects. This indicates reduction of miR-132 levels as a possible treatment of hepatic steatosis.

scholarly journals The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1281
Author(s):  
Valentina Cossiga ◽  
Vincenzo Lembo ◽  
Cecilia Nigro ◽  
Paola Mirra ◽  
Claudia Miele ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Plant Extracts ◽  
Elaeis Guineensis ◽  
Low Density Lipoprotein ◽  
Liver Steatosis ◽  
Density Lipoprotein ◽  
Coffea Canephora ◽  
Standard Diet ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

scholarly journals Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Hiroe Go ◽  
Jin Ah Ryuk ◽  
Hye Won Lee ◽  
In Sil Park ◽  
Ki-Jung Kil ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Cholesterol Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protein Levels ◽  
Related Disease

The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. Inin vivostudy using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activityin vitro. These observations support the idea that Sagunja-tang is bioavailable bothin vivoandin vitroand could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.

scholarly journals Protection against Fatty Liver but Normal Adipogenesis in Mice Lacking Adipose Differentiation-Related Protein

2006 ◽  
Vol 26 (3) ◽  
pp. 1063-1076 ◽  
Author(s):  
Benny Hung-Junn Chang ◽  
Lan Li ◽  
Antoni Paul ◽  
Susumu Taniguchi ◽  
Vijayalakshmi Nannegari ◽  
...  
Keyword(s):  
Fatty Liver ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Uptake ◽  
Related Protein ◽  
Outer Leaflet ◽  
Adipose Differentiation ◽  
Deficient Mice

ABSTRACT Adipose differentiation-related protein (ADFP; also known as ADRP or adipophilin), is a lipid droplet (LD) protein found in most cells and tissues. ADFP expression is strongly induced in cells with increased lipid load. We have inactivated the Adfp gene in mice to better understand its role in lipid accumulation. The Adfp-deficient mice have unaltered adipose differentiation or lipolysis in vitro or in vivo. Importantly, they display a 60% reduction in hepatic triglyceride (TG) and are resistant to diet-induced fatty liver. To determine the mechanism for the reduced hepatic TG content, we measured hepatic lipogenesis, very-low-density lipoprotein (VLDL) secretion, and lipid uptake and utilization, all of which parameters were shown to be similar between mutant and wild-type mice. The finding of similar VLDL output in the presence of a reduction in total TG in the Adfp-deficient liver is explained by the retention of TG in the microsomes where VLDL is assembled. Given that lipid droplets are thought to form from the outer leaflet of the microsomal membrane, the reduction of TG in the cytosol with concomitant accumulation of TG in the microsome of Adfp −/− cells suggests that ADFP may facilitate the formation of new LDs. In the absence of ADFP, impairment of LD formation is associated with the accumulation of microsomal TG but a reduction in TG in other subcellular compartments.

scholarly journals Naringin protects against non-alcoholic fatty liver disease by promoting autophagic flux and lipophagy

2021 ◽  
Author(s):  
Lingling Guan ◽  
Lan Guo ◽  
Heng Zhang ◽  
Hao Liu ◽  
Yuan Qiao ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Autophagic Flux ◽  
Mechanism Study ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Abstract Background and Purpose: The autophagic degradation of lipid droplets (LDs), termed lipophagy, is the main mechanism contributing to lipid consumption in hepatocytes. The identification of effective and safe natural compounds that target lipophagy to eliminate excess lipids may be a potential therapeutic strategy for non-alcoholic fatty liver disease (NAFLD). Here, we investigated the effects of naringin on NAFLD and the underlying mechanism. Experimental Approach: The role of naringin was investigated in mice fed a high-fat diet (HFD) to induce NAFLD, as well as in AML12 cells and primary hepatocytes stimulated by palmitate (PA). Transcription factor EB (TFEB)-knockdown AML12 cells and hepatocyte-specific TFEB-knockout mice were also used for the mechanism study. In vivo and in vitro studies were conducted using transmission electron microscopy, immunofluorescence techniques and western blot analysis. Key Results: We found that naringin treatment effectively relieved HFD-induced hepatic steatosis in mice and inhibited palmitate (PA)-induced lipid accumulation in hepatocytes. The increased p62 and LC3-II levels observed with excess lipid-support autophagosome accumulation and impaired autophagic flux. Treatment with naringin restored TFEB-mediated lysosomal biogenesis, thereby promoting the fusion of autophagosomes and lysosomes, restoring impaired autophagic flux and further inducing lipophagy. However, the knockdown of TFEB in hepatocytes or the hepatocyte-specific knockout of TFEB in mice abrogated naringin-induced lipophagy, which eliminated the therapeutic effect of naringin on hepatic steatosis. Conclusion and Implications: These results demonstrate that TFEB-mediated lysosomal biogenesis and subsequent lipophagy play essential roles in the ability of naringin to mitigate hepatic steatosis and suggest that naringin is a promising drug for treating or relieving NAFLD.

scholarly journals Lipid Profile in Alcoholic and Non Alcoholic Fatty Liver Patients

2020 ◽  
Author(s):  
Aakash Shahi ◽  
Narayan Gautam ◽  
Sanju Rawal ◽  
Uday Sharma ◽  
Archana Jayan
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Fatty Liver Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
P Value ◽  
Alcoholic Fatty Liver ◽  
Significant Difference ◽  
Alcoholic Fatty Liver Disease

Abstract Background: Fatty liver disease is a common and major chronic liver disease. It has been implicated that patients have disorders of lipid metabolism and involved in the pathogenesis of fatty liver. Lipid profile plays a very important role in diagnosis of liver diseases hence it was designed to observe relationship between lipid profile and fatty liver disease (FLD) based on ultrasonography (USG).Method and methodology: This Cross-sectional and analytical study was undertaken in the Department of Internal Medicine with collaboration of Department of Radiology and Department of Biochemistry, Universal College of Medical Sciences-Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from March 2019 to February 2020 in total 100 patients diagnosed with FLD by USG.Result: In 100 cases, the male to female ratio was 1.8:1. 56% of the total cases presented with alcoholic fatty liver disease (AFLD) while remaining 44% with non alcoholic fatty liver disease (NAFLD). The spectrum of lipid abnormality was observed with increased total cholesterol (TC), Low Density Lipoprotein (LDL), increased triglycerides (TG) and Very Low Density Lipoprotein (VLDL) in AFLD cases as compared to NAFLD cases. However, it has been observed that TG/HDL and Non-HDL/HDL were higher in NAFLD as compared to AFLD. There was statistical significant difference in HDL (p-value: 0.019) between alcoholic fatty liver disease grade 1 (AFLG1) and non-alcoholic fatty liver disease grade 1 (NAFLG1). Moreover, it was observed statistical significant difference in HDL between AFLG2 and NAFLG2 (p-value: 0.012).Conclusion:Elevated level of TG and decreased HDL has been implicated in the precipitation of the occlusive vascular disease. These parameters in conjunction with Non-HDL/HDL and TG/HDL can be useful in early screening and monitoring of dyslipidemia in the fatty liver patients to prevent cardiovascular diseases.

scholarly journals Impact of raw cocoa and chocolate on lipid profile and liver function in alcohol-induced toxicity Wister rats

2017 ◽  
Vol 5 (2) ◽  
pp. 254
Author(s):  
Alaa Saleh ◽  
Murwan Sabahelkhier
Keyword(s):  
Fatty Liver ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Treated Group ◽  
Positive Control ◽  
Alcoholic Fatty Liver ◽  
Alcohol Group ◽  
High Doses ◽  
The Impact ◽  
Positive Controls

The aim of study is to evaluate the impact of raw cocoa and processed cocoa (galaxy chocolate) in the treatment of alcoholic fatty liver compare to prednisolone drug as common medication to treat fatty liver and carried out in Al-Neelain University in 2016. Eighteen female Wister rats were classified into six groups: Group one represented negative (H2O), Group two positive controls (0.5 ml/40% alcohol), Group three represented doses of 0.67g\kg raw cocoa, Group four represented dose of 1.35 g/kg raw cocoa, Group five represent dose of 5.4 g/kg galaxy chocolate, Group six received dose of 4.8 mg/kg prednisolone. The results show that the cocoa with low and high doses, galaxy chocolate and prednisolone significantly reduce the ALT, AST and GGT, and a significant decrease in the ALT level after administration of prednisolone drug when compared high cocoa dose group. Whereas, Galaxy chocolate significantly reduce the AST compared to low dose cocoa treated group. Also there is a significant increase in HDL and decrease in Total cholesterol, Triglycerol and low density lipoprotein in all treated groups compared to positive control. The ratio between Triglycerol: HDL and LDL: HDL show a significant reduction in group treated with galaxy chocolate compared to other treated groups. The results concluded that, cocoa in both forms raw and processed are efficient in the treatment of alcoholic fatty liver in comparison with prednisolone drug.

Binding and Uptake of 125Iodine-Labelled, Oxidized Low Density Lipoprotein by Macrophages: Comparism of the Effects of a-Tocopherol, Probucol, Pyridoxal-5'-phosphate and Magnesium-pyridoxal-5'-phosphate-glutamate

1997 ◽  
Vol 52 (1-2) ◽  
pp. 97-104 ◽  
Author(s):  
Daniela Selmer ◽  
Reingard Senekowitsch-Schmidtke ◽  
W. Schneider ◽  
E. F. Elstner
Keyword(s):  
Specific Binding ◽  
Low Density Lipoprotein ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protective Effects ◽  
Oxidized Low Density Lipoprotein ◽  
Unspecific Binding

Abstract Specific and unspecific binding and uptake (internalization) by macrophages of 125iodine -labelled, copper-oxidized human low density lipoprotein is differently influenced by the anti­ oxidants α-tocopherol (α-Toc), probucol (Prob), pyridoxal-5'-phosphate (PP) and the magnesium-pyridoxal-5'-phosphate glutamate complex (MPPG). Binding as well as internalization, mediated by the so-called "scavenger receptor" is lower in the presence of MPPG whereas both specific binding and internalization are enhanced. The comparison of the effects in vitro allows a rating of the potentially anti-atherogenic and thus protective effects of the tested substances as follows: MPPG > PP > α-Toc > Prob.

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