Effects of pomegranate peel polyphenols on lipid accumulation and cholesterol metabolic transformation in L-02 human hepatic cells via the PPARγ-ABCA1/CYP7A1 pathway

2016 ◽  
Vol 7 (12) ◽  
pp. 4976-4983 ◽  
Author(s):  
Ou Lv ◽  
Lifang Wang ◽  
Jianke Li ◽  
Qianqian Ma ◽  
Wei Zhao
Keyword(s):  
Bile Acid ◽  
Lipid Accumulation ◽  
Cell Model ◽  
Hepatic Cell ◽  
Total Bile Acid ◽  
Lipid Lowering ◽  
Pomegranate Peel ◽  
Hepatic Cells ◽  
Metabolic Transformation ◽  
Lipid Lowering Effect

PPPs, PC and PEA in different concentrations were found to decrease the total cholesterol (TC) content and increase the total bile acid (TBA) content of a human hepatic cell model, and so possess a lipid-lowering effect.

scholarly journals Lnc027912 Reduces Lipid Accumulation Through Akt/MTOR/SREBP1C Axis in Hepatic Cells

2022 ◽  
Author(s):  
Kaifei Chu ◽  
Niannian Zhao ◽  
Rong Feng ◽  
Li Zhang ◽  
Xudong Hu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Western Blot ◽  
Lipid Accumulation ◽  
Cholesterol Metabolism ◽  
Cell Model ◽  
Luciferase Reporter ◽  
Hepatic Cells ◽  
Gene Assay ◽  
Signaling Axis

Abstract Background: Various metabolism diseases are closely related to lipid metabolism disorder, but long noncoding-RNAs (lncRNA) involve in regulating function of lipid was limited elucidated. Previous our work have found that lnc027912 involve in cholesterol metabolism. Here, we further explore the role of lipid metabolism-associated lncRNA-lnc027912 in oleic acid- (OA) and palmitic acid (PA)-induced hepatic cells. Methods: The overexpression of lnc027912 cell model was constructed by using virus particles transfection, and the level of lnc027912 in AML12 cells were detected by RT-qPCR. High fat cell model was established by treating AML12 cells with OA and PA, and the level of lipid drops was detected by Oil red O staining and triglyceride analyze Kit. The lipid metabolism related-genes, such as SREBP1C, FAS, PPARγ, MTTP, ApoE and ApoC3 level, was detected using RT-qPCR and Western blot. The role of SREBP1C in lipid metabolism was further analyzed using double luciferase reporter gene assay and Immunofluorescence. The Akt/mTOR signal pathway related genes was detected by Western blot. Results: We found that TG level was inhibited in overexpression of lnc027912 cell. Upregulated lnc027912 of AML12 cells treated with OA and PA showed a significant decrease in lipid accumulation and TG levels. Furthermore, overexpression of lnc027912, the lipid biosynthesis genes of SREBP1C, FAS and PPARγ was significantly decreased and a significant increase in expression of MTTP and ApoE. Interestingly, lnc027912 inhibited Akt/mTOR signaling axis and decreased SREBP1C transit into nucleus and the promoter activity of SREBP1C and regulated expression of its targets. Conclusions: Our study revealed a new insights into the molecular function of lnc027912 in lipid metabolism by Akt/mTOR/SREBP1C signaling axis and highlights the potential of lnc027912 as a new therapeutic target for lipid disorder diseases (such as, NAFLD).

scholarly journals Autoantibodies directed against apolipoprotein A-1 as a potential contributor to non-alcoholic fatty liver disease

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Pagano ◽  
D Alfaiate ◽  
C Juillard ◽  
M Frias ◽  
A Magenta ◽  
...  
Keyword(s):  
Liver Disease ◽  
Lipid Accumulation ◽  
Hepatic Cell ◽  
Alcoholic Fatty Liver ◽  
Hepatic Cells ◽  
Apolipoprotein A ◽  
Tnf Α ◽  
Potential Contributor ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-Alcoholic Fatty Liver Disease (NAFLD) represents an increasing cause of liver disease worldwide. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in these patients. Although NAFLD pathophysiology is not fully understood alterations in fat metabolism seem to play a role. Autoantibodies against apolipoprotein A-1 (anti-apoA-1 IgG) are a novel cardiovascular risk factor to which have been recently attributed a metabolic role in addition to a well-established macrophage-mediated inflammatory effect and have a function as a disruptor of the cholesterol pathway. Purpose This study aims at evaluating a possible role of anti-apoA-1 IgG in NAFLD. Methods Serum from 137 NAFLD patients were tested for anti-apoA-1 IgG prevalence. In vitro, SREBP1, SREBP2 expressions were assessed in the human hepatic cell line HepaRG by western blot analysis and bodipy staining was used to evaluate the lipid droplet content. Mescoscale technology platform was used to measure TNF-α, IL-6 and IL-8 cytokines/chemokines in HepaRG supernatants. Oil Red O staining was used to detect lipid accumulation in liver sections from ApoE−/− mice. Results Elevated anti-apoA-1 IgG seropositivity was found in patients with NAFLD (46%). In vitro, anti-apoA-1 IgG and not control IgG induced lipid accumulation in hepatic cells (5.9 vs 2.5, P=0.0008) and this lipid overload was associated with a high SREBP1 but not SREBP2 expression. Furthermore, anti-apoA-1 IgG and not control antibodies caused a significant large increase of the proinflammatory cytokines IL-6 (680 vs. 163 pg/mL, P=0.03) and TNF-α (391 vs 266 pg/mL, P=0.04) as well as of the chemokine IL-8 (174.1 vs. 72.6 ng/mL, P=0.03) detected in the hepatic cell supernatants. In vivo, anti-apoA-1 IgG and not control IgG also induced higher lipid accumulation in the livers of ApoE−/− mice (1.23 vs 0.53, P=0.03). Conclusion Anti-apoA-1 IgG are frequent in NAFLD, cause a strong inflammatory response and promote lipid accumulation through SREBP1 activation in human hepatic cells. We hypothesize that anti-apoA1 IgG may be a potential contributor in the development of NAFLD. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Geneva University Hospital

scholarly journals Bai-Hu-Jia-Ren-Shen-Tang Decoction Reduces Fatty Liver by Activating AMP-Activated Protein Kinase In Vitro and In Vivo

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Hui-Kang Liu ◽  
Tzu-Min Hung ◽  
Hsiu-Chen Huang ◽  
I-Jung Lee ◽  
Chia-Chuan Chang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Serum Triglyceride ◽  
Total Lipid Content ◽  
Lipid Lowering ◽  
Acid Oxidation ◽  
Lowering Effect ◽  
Amp Activated Protein Kinase ◽  
Lipid Lowering Effect

Obesity and associated conditions, such as type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. In Asian traditional medicine, Bai-Hu-Jia-Ren-Shen-Tang (BHJRST) is widely used in diabetes patients to reduce thirst. However, whether it has a therapeutic effect on T2DM or NAFLD is not known. The aim of this study was to examine whether BHJRST had a lipid-lowering effect using a HuS-E/2 cell model of fatty liver induced by palmitate and in a db/db mouse model of dyslipidemia. Incubation of HuS-E/2 cells with palmitate markedly increased lipid accumulation and expression of adipose triglyceride lipase (ATGL), which is involved in lipolysis. BHJRST significantly decreased lipid accumulation and increased ATGL levels and phosphorylation of AMP-activated protein kinase (AMPK) and its primary downstream target, acetyl-CoA carboxylase (ACC), which are involved in fatty acid oxidation. Furthermore, after twice daily oral administration for six weeks, BHJRST significantly reduced hepatic fat accumulation in db/db mice, as demonstrated by increased hepatic AMPK and ACC phosphorylation, reduced serum triglyceride levels, and reduced hepatic total lipid content. The results show that BHJRST has a lipid-lowering effect in the liver that is mediated by activation of the AMPK signaling pathway.

CD36 and DGAT2 facilitates the lipid-lowering effect of chitooligosaccharides via fatty acid intake and triglyceride synthesis signaling

2021 ◽  
Author(s):  
Xin Shen ◽  
Xinyi Liang ◽  
Xiaoguo Ji ◽  
Jiangshan You ◽  
Xinye Zhuang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Total Cholesterol ◽  
Lipid Accumulation ◽  
Lipid Lowering ◽  
Fatty Acid Intake ◽  
Triglyceride Synthesis ◽  
Acid Intake ◽  
Lowering Effect ◽  
The Impact ◽  
Lipid Lowering Effect

This study examined the impact of chitobiose (GlcN)2 and chitotriose (GlcN)3 on lipid accumulation modification and its inhibitory functionality. (GlcN)2 and (GlcN)3 was found to significantly inhibit the total cholesterol...

scholarly journals The Metabolic Changes of Artesunate and Ursolic Acid on Syrian Golden Hamsters Fed with the High-Fat Diet

Molecules ◽  
2020 ◽  
Vol 25 (6) ◽  
pp. 1392
Author(s):  
Shichen Pu ◽  
Yumin Liu ◽  
Shan Liang ◽  
Pin Liu ◽  
Hongmei Qian ◽  
...  
Keyword(s):  
Ursolic Acid ◽  
High Fat Diet ◽  
Metabolic Changes ◽  
Lipid Lowering ◽  
High Fat ◽  
Flight Mass Spectrometry ◽  
Syrian Golden Hamsters ◽  
Metabolic Transformation ◽  
Group A ◽  
Lipid Lowering Effect

Artesunate was well known as an antimalarial drug. Our previous research found that it has hypolipidemia effects in rabbits fed with a high-fat diet, especially combined with ursolic acid. In this study, we reconfirmed the lipid-lowering effect of artesunate and ursolic acid in hamsters and analyzed the metabolic changes using gas chromatography time-of-flight mass spectrometry (GC/TOF MS). Compared with the model group, a variety of different metabolites of artesunate and ursolic acid, alone or in combination, were found and confirmed. These differential metabolites, including fatty acids, lipids, and amino acids, were involved in lipid metabolism, energy metabolism, and amino acid metabolism. It indicated that two agents of artesunate and ursolic acid could attenuate or normalize the metabolic transformation on these metabolic pathways.

Synthesis, Characterization and In vitro Evaluation of N-Substituted- Sulfomoyl-Phenyl-Amino Carboxylic Acid Derivatives as Squalene Synthase Inhibitors

2019 ◽  
Vol 15 (4) ◽  
pp. 415-426
Author(s):  
Avani B. Chokshi ◽  
Mahesh T. Chhabria ◽  
Pritesh R. Desai
Keyword(s):  
Carboxylic Acid ◽  
Cell Line ◽  
Hepatic Cell ◽  
Squalene Synthase ◽  
Lipid Lowering ◽  
Assay Method ◽  
Aromatic Substituent ◽  
Hepatic Cell Line ◽  
Amino Carboxylic Acid

Background:Squalene Synthase is one of the cholesterol biosynthetic pathway enzymes, inhibition of which produces potent lipid lowering action. A variety of chemical classes have been evaluated for its inhibition to provide alternate antihyperlipidemic agents to statins.Methods:A series of N-substituted-sulfomoyl-phenyl-amino carboxylic acid derivatives were designed through pharmacophore modelling as Squalene Synthase inhibitors. We report here the synthesis, characterization and in vitro pharmacological screening of the designed molecules as Squalene synthase inhibitors. The target molecules were synthesized by a simple procedure and each molecule was characterized by IR, Mass, 1HNMR and 13CNMR spectroscopic techniques. As a primary site of action for cholesterol biosynthesis is liver, each of the molecules were first screened for in vitro cytotoxicity over human hepatic cell line (HepG2) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay method. The enzyme inhibition assay was performed on cell lysates prepared from HepG2 cells by Human Squalene Synthase ELISA kit, where test compounds were added in the nontoxic concentrations only.Results:Compound 5f was found to be most potent with the IC50 value of 11.91 µM. The CTC50 value for 5f on human hepatic cell line was > 1000 µM so it was considered that the compound was relatively safe and might be free of hepatotoxicity.Conclusion:From the results of our studies, it was observed that compounds with poly nuclear aromatic or hetero aromatic substituent on a side chain were more potent enzyme inhibitors and a distance of 4-5 atoms is optimum between amide nitrogen and hydroxyl group of carboxylic acid.

scholarly journals A pharmacokinetics–pharmacodynamics study of single-dose total glucosides of paeony capsule on reducing serum total bile acid in hepatic injury rats

2021 ◽  
Vol 59 (1) ◽  
pp. 769-777
Author(s):  
Ninghua Jiang ◽  
Bohong Zheng ◽  
Yihan Feng ◽  
Lei Yin ◽  
Yuanrong Liu ◽  
...  
Keyword(s):  
Single Dose ◽  
Bile Acid ◽  
Hepatic Injury ◽  
Total Bile Acid ◽  
Total Glucosides Of Paeony
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