scholarly journals Rosmarinic acid attenuates hepatic steatosis by modulating ER stress and autophagy in oleic acid-induced HepG2 cells

RSC Advances ◽  
2018 ◽  
Vol 8 (47) ◽  
pp. 26656-26663 ◽  
Author(s):  
Govindaraj Jayanthy Balachander ◽  
Sorimuthupillai Subramanian ◽  
Kaliappan Ilango
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
Rosmarinic Acid ◽  
Hepg2 Cells ◽  
Liver Disorders

Non-alcoholic fatty acid disease (NAFLD) has become an emerging entity of liver disorders worldwide.

scholarly journals Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chian-Jiun Liou ◽  
Shu-Ju Wu ◽  
Szu-Chuan Shen ◽  
Li-Chen Chen ◽  
Ya-Ling Chen ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Liver Lipid ◽  
Obese Mice ◽  
Alcoholic Fatty Liver

Abstract Background Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. Methods HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. Results Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. Conclusions These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.

scholarly journals Poria cocus Wolf Extract Ameliorates Hepatic Steatosis through Regulation of Lipid Metabolism, Inhibition of ER Stress, and Activation of Autophagy via AMPK Activation

2019 ◽  
Vol 20 (19) ◽  
pp. 4801 ◽  
Author(s):  
Ji-Hyun Kim ◽  
Hyun A Sim ◽  
Dae Young Jung ◽  
Eun Yeong Lim ◽  
Yun Tai Kim ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Er Stress ◽  
Hepatic Steatosis ◽  
Fatty Acid Oxidation ◽  
Hepg2 Cells ◽  
Acid Oxidation ◽  
Pachymic Acid ◽  
Metabolism Inhibition

Poria cocos Wolf (PCW) is an edible, pharmaceutical mushroom with remarkable biological properties including anti-tumor, anti-inflammation, anti-oxidation, anti-ageing, and anti-diabetic effects. In the current study, we investigated the effects of PCW extract on hepatic steatosis under in vitro and in vivo conditions, and elucidated the underlying mechanisms. In this study, a mixture of HepG2 cells treated with free fatty acid (FFA)—palmitic and oleic acid—and high-fat diet (HFD)-fed obese mice were used; in this background, the triglyceride (TG) levels in HepG2 cells and mice liver were measured, and the expression levels of genes associated with lipogenesis, fatty acid oxidation, endoplasmic reticulum (ER) stress, and autophagy were determined. Treatment of HepG2 cells with FFA enhanced intracellular TG levels in HepG2 cells, but co-treatment with PCW significantly attenuated the TG levels. Notably, PCW significantly enhanced the phosphorylation of AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), and sterol regulatory element-binding protein-1c (SREBP-1c) in FFA-treated HepG2 cells. PCW downregulated the expression of lipogenesis-related genes, but upregulated the expression of genes associated with fatty acid oxidation. Further, PCW inhibited FFA-induced expression of ER stress markers and induced autophagy proteins. However, inhibition of AMPK significantly attenuated the beneficial effects of PCW in HepG2 cells. Moreover, PCW efficiently decreased HFD-induced hepatic TG accumulation in vivo and increased the phosphorylation of hepatic AMPK. Three compounds present in PCW including poricoic acid, pachymic acid, and ergosterol, significantly decreased FFA-induced increase in intracellular TG levels, consistent with increased AMPK phosphorylation, suggesting that poricoic acid, pachymic acid, and ergosterol are responsible for PCW-mediated amelioration of hepatic steatosis. Taken together, these results demonstrated that PCW ameliorates hepatic steatosis through the regulation of lipid metabolism, inhibition of ER stress, and activation of autophagy in an AMPK-dependent manner. This suggested that PCW can be potentially used for the treatment of hepatic steatosis.

scholarly journals Aqueous Extract of Pepino Leaves Ameliorates Palmitic Acid-Induced Hepatocellular Lipotoxicity via Inhibition of Endoplasmic Reticulum Stress and Apoptosis

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 903
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Charng-Cherng Chyau ◽  
Zhi-Hong Wang ◽  
Jing-Hsien Chen
Keyword(s):  
Fatty Acid ◽  
Palmitic Acid ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Target Genes ◽  
Liver Lipid ◽  
Antioxidant Response ◽  
Long Chain Fatty Acid ◽  
Nrf2 Expression

Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.

scholarly journals Artemisia iwayomogiplusCurcuma longaSynergistically Ameliorates Nonalcoholic Steatohepatitis in HepG2 Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Hyeong-Geug Kim ◽  
Sung-Bae Lee ◽  
Jin-Seok Lee ◽  
Won-Young Kim ◽  
Seung-Hoon Choi ◽  
...  
Keyword(s):  
Er Stress ◽  
Nonalcoholic Steatohepatitis ◽  
Hepg2 Cells ◽  
Curcuma Longa ◽  
Water Extract ◽  
Underlying Mechanism ◽  
Liver Disorders ◽  
Artemisia Iwayomogi ◽  
Clinical Potential ◽  
Intracellular Triglyceride

The combination ofArtemisia iwayomogiandCurcuma longaradix is frequently prescribed for liver diseases in TKM. However, the synergic effects of the two herbs on nonalcoholic steatohepatitis (NASH) have not yet been studied. Therefore, we investigated the anti-NASH effects of the water extract ofA. iwayomogi(AI),C. longaradix (CL), and combination of the two herbs (ACE). Hepatic steatosis and NASH were induced in HepG2 cells by treatment with palmitic acid (PA, for 6 h) with/without pretreatment of ACE (25 or 50 μg/mL), AI (50 or 100 μg/mL), CL (50 or 100 μg/mL), curcumin (5 μg/mL), or scopoletin (5 μg/mL). The PA treatment (200 μM) drastically altered intracellular triglyceride levels, total cholesterol, and expression levels of genes related to lipid metabolism (CD36, SREBP1c, PPAR-γ, and PPAR-α), whereas pretreatment with ACE significantly attenuated these alterations. ACE also protected HepG2 cells from PA- (300 μM-) induced endoplasmic reticulum (ER) stress and apoptosis and attenuated the related key molecules including GRP78, eIF2, and CHOP, respectively. In conclusion, we found synergic effects ofA. iwayomogiandC. longaon NASH, supporting the clinical potential for fatty liver disorders. In addition, modulation of ER stress-relative molecules would be involved in its underlying mechanism.

Effect and mechanism of ginsenoside Rg1-regulating hepatic steatosis in HepG2 cells induced by free fatty acid

2020 ◽  
Vol 84 (11) ◽  
pp. 2228-2240
Author(s):  
Yue Gao ◽  
Shujun Zhang ◽  
Jiajun Li ◽  
Jinqiu Zhao ◽  
Qing Xiao ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Free Fatty Acid ◽  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Ginsenoside Rg1

scholarly journals Differential Lipotoxic Effects of Palmitate and Oleate in Activated Human Hepatic Stellate Cells and Epithelial Hepatoma Cells

2016 ◽  
Vol 39 (4) ◽  
pp. 1648-1662 ◽  
Author(s):  
Alexandra M. Hetherington ◽  
Cynthia G. Sawyez ◽  
Emma Zilberman ◽  
Alexandra M. Stoianov ◽  
Debra L. Robson ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Er Stress ◽  
Hepatic Stellate Cells ◽  
Hepg2 Cells ◽  
Stellate Cells ◽  
Hepatoma Cells ◽  
Surrounding Tissue ◽  
High Oleate ◽  
Activated Hepatic Stellate Cells

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) progression to fibrosis, cirrhosis and hepatocellular carcinoma, alters the cellular composition of this organ. During late-stage NAFLD, fibrotic and possibly cancerous cells can proliferate and, like normal hepatocytes, are exposed to high concentrations of fatty acids from both surrounding tissue and circulating lipid sources. We hypothesized that primary human activated hepatic stellate cells and epithelial hepatoma (HepG2) cells respond differently to lipotoxic conditions, and investigated the mechanisms involved. Methods: Primary activated hepatic stellate cells and HepG2 cells were exposed to pathophysiological concentrations of fatty acids and comparative studies of lipid metabolic and stress response pathways were performed. Results: Both cell types remained proliferative during exposure to a combination of palmitate plus oleate reflective of the general saturated versus unsaturated fatty acid composition of western diets. However, exposure to either high palmitate or high oleate alone induced cytotoxicity in activated stellate cells, while only palmitate caused cytotoxicity in HepG2 cells. mRNA microarray and biochemical comparisons revealed that stellate cells stored markedly less fatty acids as neutral lipids, and had reduced capacity for beta-oxidation. Similar to previous observations in HepG2 cells, palmitate, but not oleate, induced ER stress and actin stress fiber formation in activated stellate cells. In contrast, oleate, but not palmitate, induced the inflammatory signal TXNIP, decreased cytoskeleton proteins, and decreased cell polarity preceding cell death in activated stellate cells. Conclusions: Palmitate-induced lipotoxicity was associated with ER stress pathways in both primary activated hepatic stellate cells and epithelial hepatoma cells, whereas high oleate caused lipotoxicity only in activated stellate cells, possibly through a distinct mechanism involving disruption of cytoskeleton components. This may have implications for optimal dietary fatty acid compositions during various stages of NAFLD.

Liv.52 up-regulates cellular antioxidants and increase glucose uptake to circumvent oleic acid induced hepatic steatosis in HepG2 cells

Phytomedicine ◽  
2012 ◽  
Vol 19 (13) ◽  
pp. 1156-1165 ◽  
Author(s):  
Satyakumar Vidyashankar ◽  
L.M. Sharath Kumar ◽  
Vandana Barooah ◽  
R. Sandeep Varma ◽  
Krishna S. Nandakumar ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Glucose Uptake ◽  
Hepatic Steatosis ◽  
Hepg2 Cells ◽  
Increase Glucose Uptake ◽  
Cellular Antioxidants

scholarly journals Alisol A 24-Acetate Prevents Hepatic Steatosis and Metabolic Disorders in HepG2 Cells

2016 ◽  
Vol 40 (3-4) ◽  
pp. 453-464 ◽  
Author(s):  
Lu Zeng ◽  
WaiJiao Tang ◽  
JinJin Yin ◽  
LiJuan Feng ◽  
Yabing Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Metabolic Disorders ◽  
Therapeutic Effects ◽  
Group Model ◽  
Mrna Levels ◽  
Tnf Α ◽  
Oil Red O

Background: Non-alcoholic fatty liver disease (NAFLD) is closely associated with metabolic disorders including hepatic lipid accumulation and inflammation. Alisol A 24-acetate, a triterpene from Alismatis rhizome, has multiple biologic activities such as hypolipidemic, anti-inflammatory and anti-diabetic. Thus we hypothesized that Alisol A 24 -acetate would have effect on NAFLD. The present study was conducted to investigate the therapeutic effects and potential mechanisms of Alisol A 24-acetate against hepatic steatosis in a free fatty acids (FFAs) induced NAFLD cell model. Methods: This study was divided into four groups including Control group, Model group (FFA group), Alisol A 24-acetate (FFA+A) group, Fenofibrate (FFA+F) group. Preventive role of Alisol A 24-acetate was evaluated using 10µM Alisol A 24-acetate plus 1 mM FFA (oleate:palmitate=2:1) incubated with HepG2 cells for 24 h, which was determined by Oil Red O Staining, Oil Red O based colorimetric assay and intracellular triglyceride (TG) content. Besides, the inflammatory cytokines tumor necrosis factor (TNF)- α, interleukin (IL)-6 levels as well as the protein and mRNA expressions that were involved in fatty acid synthesis and oxidation including Adiponectin, AMP-activated protein kinase (AMPK) α, peroxisome proliferator-activated receptor (PPAR) α, sterol regulatory element binding protein 1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1) and acyl coenzyme A oxidase 1 (ACOX1) were detected. Results: Alisol A 24-acetate significantly decreased the numbers of lipid droplets, Oil Red O lipid content, and intracellular TG content. Besides, inflammatory cytokines TNF-α, IL-6 levels were markedly inhibited by Alisol A 24-acetate. Furthermore, Alisol A 24-acetate effectively increased the protein and mRNA expressions of Adiponectin, the phosphorylation of AMPKα, CPT1 and ACOX1, whereas decreased SREBP-1c, the phosphorylation of ACC and FAS at both protein and mRNA levels. However, there was no significant effect on the protein and mRNA expressions of PPARα by Alisol A 24-acetate. Conclusions: These results demonstrated that Alisol A 24-acetate effectively ameliorated hepatic steatosis likely through Adiponectin, which activated AMPKα signaling pathways via down-regulating SREBP-1c, ACC, FAS and up-regulating CPT1 and ACOX1, and inhibited inflammation. Thereby, Alisol A 24-acetate could be a promising candidate for the treatment of NAFLD.

scholarly journals An Experimental Model of Hepatic Steatosis to Detect Lipid Accumulation

2018 ◽  
pp. 1-10
Author(s):  
Maryam Ammani Lawal ◽  
Gregory Elayeche Oko ◽  
Emmanuel Paul Okoi ◽  
Khuyen Thi Kim Vo ◽  
Shuaib Samirah Isah
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Hepatic Steatosis ◽  
Experimental Model ◽  
Hepg2 Cells ◽  
Colorimetric Detection ◽  
Acid Media ◽  
Alcoholic Fatty Liver ◽  
Increased Risk

Obesity is associated with an increased risk of metabolic syndromes such as type 2 diabetes, insulin resistance, dyslipidaemia and non-alcoholic fatty liver disease. Obesity occurs as a result of an imbalance between food intake and energy expenditure leading to excessive accumulation of adipose tissue. NAFLD is the most common liver condition and related to the resistance of insulin. Insulin resistance is associated with an increased influx of lipid into the liver promoting accumulation of hepatic triglyceride. This study aims to develop an experimental model of hepatic steatosis with lipid over-accumulation. HepG2 cells were cultured for 24 hours in free fatty acid media (1:2 palmitic acid and oleic acid respectively). Intracellular lipid content and lipotoxicity were determined by oil red O staining followed by colorimetric detection. This experiment was accomplished by defining the experimental conditions of lipid exposure that leads to significant intracellular fat accumulation in the absence of lipotoxicity with 1 mM of free fatty acid media. As a result, oleic and palmitic acids could be over-accumulated in HepG2 cells. 1 mM free fatty acid media did not affect the cell integrity and did not cause lipotoxicity of the cells.

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