scholarly journals Free Fatty Acids Impair FGF21 Action in HepG2 Cells

2015 ◽  
Vol 37 (5) ◽  
pp. 1767-1778 ◽  
Author(s):  
Mohamed Asrih ◽  
Christophe Montessuit ◽  
Jacques Philippe ◽  
François R. Jornayvaz
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Free Fatty Acids ◽  
Hepg2 Cells ◽  
Lipid Lowering ◽  
Fibroblast Growth Factor 21 ◽  
Beneficial Effects ◽  
Positive Effects

Background/Aims: Fibroblast growth factor 21 (FGF21) is a key mediator of glucose and lipid metabolism. However, the beneficial effects of exogenous FGF21 administration are attenuated in obese animals and humans with elevated levels of circulating free fatty acids (FFA). Methods: We investigated in vitro how FFA impact FGF21 effects on hepatic lipid metabolism. Results: In the absence of FFA, FGF21 reduced lipogenesis and increased lipid oxidation in HepG2 cells. Inhibition of lipogenesis was associated with a down regulation of SREBP-1c, FAS and SCD1. The lipid-lowering effect was associated with AMPK and ACC phosphorylation, and up regulation of CPT-1α expression. Further, FGF21 treatment reduced TNFα gene expression, suggesting a beneficial action of FGF21 on inflammation. In contrast, the addition of FFA abolished the positive effects of FGF21 on lipid metabolism. Conclusion: In the absence of FFA, FGF21 improves lipid metabolism in HepG2 cells and reduces the inflammatory cytokine TNFα. However, under high levels of FFA, FGF21 action on lipid metabolism and TNFα gene expression is impaired. Therefore, FFA impair FGF21 action in HepG2 cells potentially through TNFα.

scholarly journals Strawberry and Achenes Hydroalcoholic Extracts and Their Digested Fractions Efficiently Counteract the AAPH-Induced Oxidative Damage in HepG2 Cells

2018 ◽  
Vol 19 (8) ◽  
pp. 2180 ◽  
Author(s):  
María Ariza ◽  
Tamara Forbes-Hernández ◽  
Patricia Reboredo-Rodríguez ◽  
Sadia Afrin ◽  
Massimiliano Gasparrini ◽  
...  
Keyword(s):  
Biological Activity ◽  
Oxidative Damage ◽  
Hepg2 Cells ◽  
In Vitro Digestion ◽  
Protective Effects ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Digestion Process ◽  
Phytochemical Compounds

Strawberry fruits are highly appreciated by consumers worldwide due to their bright red color, typical aroma, and juicy texture. While the biological activity of the complete fruit has been widely studied, the potential beneficial effects of the achenes (commonly named seeds) remain unknown. In addition, when raw fruit and achenes are consumed, the digestion process could alter the release and absorption of their phytochemical compounds, compromising their bioactivity. In the present work, we evaluated the protective effects against oxidative damage of nondigested and digested extracts from strawberry fruit and achenes in human hepatocellular carcinoma (HepG2) cells. For that purpose, cells were treated with different concentration of the extracts prior to incubation with the stressor agent, AAPH (2,2′-azobis(2-amidinopropane) dihydrochloride). Subsequently, intracellular accumulation of reactive oxygen species (ROS) and the percentage of live, dead, and apoptotic cells were determined. Our results demonstrated that all the evaluated fractions were able to counteract the AAPH-induced damage, suggesting that the achenes also present biological activity. The positive effects of both the raw fruit and achenes were maintained after the in vitro digestion process.

scholarly journals Elevated free fatty acids affect bovine granulosa cell function: a molecular cue for compromised reproduction during negative energy balance

2019 ◽  
Vol 8 (5) ◽  
pp. 493-505 ◽  
Author(s):  
Arpna Sharma ◽  
Vijay Simha Baddela ◽  
Frank Becker ◽  
Dirk Dannenberger ◽  
Torsten Viergutz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Energy Balance ◽  
Free Fatty Acids ◽  
Dairy Cows ◽  
Combination Treatment ◽  
Follicular Fluid ◽  
Negative Energy

High-yielding dairy cows postpartum face the challenge of negative energy balance leading to elevated free fatty acids levels in the serum and follicular fluid thus affecting the ovarian function. Here, we investigated effects of physiological concentrations of palmitic acid (PA), stearic acid (SA) and oleic acid (OA) on the viability, steroid production and gene expression in a bovine granulosa cell (GC) culture model. Treatment with individual and combined fatty acids increased the CD36 gene expression, while no significant apoptotic effects were observed. Both PA and SA significantly upregulated the expression of FSHR, LHCGR, CYP19A1, HSD3B1, CCND2 and increased 17β-estradiol (E2) production, while OA downregulated the expression of these genes and reduced E2. Interestingly, STAR was equally downregulated by all fatty acids and combination treatment. E2 was significantly reduced after combination treatment. To validate the effects of OA, in vivo growing dominant follicles (10–19 mm) were injected with bovine serum albumin (BSA) with/without conjugated OA. The follicular fluid was recovered 48 h post injection. As in our in vitro model, OA significantly reduced intrafollicular E2 concentrations. In addition, expression of CD36 was significantly up- and that of CYP19A1 and STAR significantly downregulated in antral GC recovered from aspirated follicles. The ovulation rates of OA-injected follicles tended to be reduced. Our results indicate that elevated free fatty acid concentrations specifically target functional key genes in GC both in vitro and in vivo. Suggestively, this could be a possible mechanism through which elevated free fatty acids affect folliculogenesis in dairy cows postpartum.

Qushi Huayu Decoction (祛湿化瘀方) inhibits protein and gene expression of cathepsin B in HepG2 Cells induced by free fatty acids

2010 ◽  
Vol 16 (6) ◽  
pp. 518-524 ◽  
Author(s):  
Qin Feng ◽  
Yang Cheng ◽  
Yi-yang Hu ◽  
Hui Zhang ◽  
Jing-hua Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Free Fatty Acids ◽  
Cathepsin B ◽  
Hepg2 Cells

scholarly journals SUN-550 CARF Through Its Lipid Lowering Effect May Play a Pivotal Role in the Development of Non-Alcoholic Fatty Liver Diseases

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Kamrul M Hasan ◽  
Meher Parveen ◽  
Alondra Pena ◽  
Amiya P Sinha-Hikim ◽  
Theodore C Friedman
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Hepg2 Cells ◽  
In Vitro Model ◽  
Lipid Lowering ◽  
Alcoholic Fatty Liver ◽  
Lowering Effect ◽  
Vitro Model ◽  
Lipid Lowering Effect

Abstract CARF (Collaborator of ARF), a member of ARF-MDM2-p53 pathway and an emerging multifunctional protein, regulates cellular fate in response to various stresses including oxidative DNA damage and replicative stresses. However, its role in metabolic syndrome (MS) and associated diseases has not been studied. This study, using our well established in vivo and in vitro model systems, examines the role of CARF in the development of non-alcoholic fatty liver disease (NAFLD). Indeed, we have found that, compared to control, CARF expression along with Sirt1, pAMPK and pACC (common biological markers of NAFLD) was significantly decreased in the nicotine and high-fat-diet (HFD) in combination or HFD alone induced fatty livers. Additionally, CARF expression was down regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis, suggesting that CARF expression is negatively regulated in MS, such as NAFLD. Our study further revealed that shRNA mediated knockdown or lentiviral mediated over expression of CARF induced or reduced endogenous fat accumulation, respectively, in HepG2 cells. We also found that overexpression of CARF lowered the exogenous fat accumulation in PA treated HepG2 cells. RNA seq analysis after CARF knockdown in HEK-293T cells further revealed that genes associated with lipid metabolism and triglyceride (TG) synthesis such as diacylglycerol O-acyltransferase2 (DGAT2), acyl-CoA synthetase long-chain family member 4 and 6 (ACSL4, ACSL6) were upregulated in CARF-depleted cells. Likewise, we also found increased expression of DGAT2 in CARF-depleted HepG2 cells, which enhanced TG synthesis. Intriguingly, consistent with the lipid lowering effects of metformin, an antidiabetic drug, we further found that CARF expression along with pAMPK and Sirt1 were significantly increased in metformin-treated HepG2 cells. However, we also found increased pACC levels in CARF over-expressing cells which was further enhanced in metformin-treated cells, suggesting, for the first time, that CARF may contribute to lipid lowering effect of metformin by inhibiting lipogenesis. We conclude that CARF has a lipid lowering effect in hepatocytes and its down regulation in response to MS perturbs lipid metabolism that may lead to the development of NAFLD.

scholarly journals Reduced Oxidative Stress Contributes to the Lipid Lowering Effects of Isoquercitrin in Free Fatty Acids Induced Hepatocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-18 ◽  
Author(s):  
Waseem Hassan ◽  
Gao Rongyin ◽  
Abdelkader Daoud ◽  
Lin Ding ◽  
Lulu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Lipid Metabolism ◽  
Free Fatty Acids ◽  
Molecular Level ◽  
Lipid Lowering ◽  
Hepatic Lipid Metabolism ◽  
Ampk Pathway ◽  
Coculture Model ◽  
And Oxidative Stress

Oxidative stress interferes with hepatic lipid metabolism at various levels ranging from benign lipid storage to so-called second hit of inflammation activation. Isoquercitrin (IQ) is widely present flavonoid but its effects on hepatic lipid metabolism remain unknown. We used free fatty acids (FFA) induced lipid overload and oxidative stress model in two types of liver cells and measured cell viability, intracellular lipids, and reactive oxygen species (ROS) within hepatocytes. In addition, Intracellular triglycerides (TG), superoxide dismutase (SOD), and malondialdehyde (MDA) were examined. A novelin vitromodel was used to evaluate correlation between lipid lowering and antioxidative activities. Furthermore, 34 major cytokines and corresponding ROS levels were analyzed in FFA/LPS induced coculture model between hepatocytes and Kupffer cells. At molecular level AMPK pathway was elucidated. We showed that IQ attenuated FFA induced lipid overload and ROS within hepatocytes. Further, IQ reversed FFA induced increase in intracellular TG SOD and MDA. It was shown that antioxidative activity of IQ correlates with its lipid lowering potentials. IQ reversed major proinflammatory cytokines and oxidative stress in FFA/LPS induced coculture model. Finally, AMPK pathway was found responsible for metabolic benefits at molecular level. IQ strikingly manifests antioxidative and related lipid lowering activities in hepatocytes.

scholarly journals The Independence of Signaling Pathways Mediating Increased Expression of Plasminogen Activator Inhibitor Type1in HepG2 Cells Exposed to Free Fatty Acids or Triglycerides

2002 ◽  
Vol 3 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Yabing Chen ◽  
David J. Schneider
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Plasminogen Activator ◽  
Hepg2 Cells ◽  
Plasminogen Activator Inhibitor ◽  
Fold Induction ◽  
Activator Inhibitor ◽  
Pai 1

We have shown that both free fatty acids (FFA) and triglycerides (TG) increase expression of plasminogen activator inhibitor type 1 (PAI-1) in vivo and in vitro. To determine signaling mechanisms responsible, HepG2 cells were exposed to FFA, emulsified TG, or the combination. The combination of FFA and TG increased PAI-1 to a greater extent than either agent alone (fold induction: 0.45mM FFA 1.7±0.2, 1000mg/dl TG 1.9±0.1, both 2.3±0.2, n=10, p<0.05 for comparison of combination with either alone). Cells transfected with PAI-1 5' flanking region containing the 4G or 5G polymorphism displayed similar activity in response to FFA, but modestly greater activity with the 4G polymorphism in response to TG (fold induction: 5G-1.28±0.14 and 4G- 1.46±0.13, n=6, p<0.05 for comparison). Deletion analyses demonstrated that FFA and TG induce PAI-1 expression through distinct regions of the promoter. Inhibition of protein kinase C inhibited the response to FFA but not TG. Accordingly, increased FFA and TG contribute to increased PAI- I through independent mechanisms.

Anti-atherosclerotic effects of fruit bioactive compounds: A review of current scientific evidence

2012 ◽  
Vol 92 (3) ◽  
pp. 407-419 ◽  
Author(s):  
Surangi H. Thilakarathna ◽  
H. P. Vasantha Rupasinghe
Keyword(s):  
Bioactive Compounds ◽  
Antioxidant Activities ◽  
Scientific Evidence ◽  
Experimental Models ◽  
Lipid Lowering ◽  
Experimental Conditions ◽  
Beneficial Effects ◽  
Positive Effects

Thilakarathna, S. H. and Rupasinghe, H. P. V. 2012. Anti-atherosclerotic effects of fruit bioactive compounds: A review of current scientific evidence. Can. J. Plant Sci. 92: 407–419. Atherosclerosis is a condition which leads to a cascade of processes involved in thickening of arterial walls as a result of fatty deposition, which can increase the risk of cardiovascular diseases. Among numerous remedies, the consumption of fruits is believed to have beneficial effects on atherosclerosis development. Various bioactive compounds are present in fruits and they have been found to be responsible for exerting these beneficial effects. Fruit flavonoids and certain terpenoids are among the most efficacious fruit bioactive compounds that have shown positive effects on different in vitro as well as in vivo research models of atherosclerosis. The mechanisms of actions of these compounds vary from exerting antioxidant activities to anti-atherogenic and lipid lowering activities, based on different experimental models. This review article briefly explains how some of the fruit bioactive compounds have affected atherosclerosis under experimental conditions.

scholarly journals Use of Network Pharmacology to Investigate the Mechanism by Which Allicin Ameliorates Lipid Metabolism Disorder in HepG2 Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Bijun Cheng ◽  
Tianjiao Li ◽  
Fenglin Li
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Hepg2 Cells ◽  
Experimental Validation ◽  
Biological Activities ◽  
Lipid Lowering ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Lipid Metabolism Disorder ◽  
Metabolism Disorder

Allicin has been well documented to exhibit a wide spectrum of biological activities, especially lipid-lowering activity, as a promising candidate for the management of nonalcoholic fatty liver disease (NALFD). However, the mechanisms underlying the therapeutic effects of allicin require further investigation. It is tempting to think of combining network pharmacology and experimental validation to investigate the mechanism by which allicin ameliorates lipid metabolism disorder in HepG2 cells. We established a cell model of hepatic steatosis induced by PA to investigate the antisteatotic effects of allicin. The studies showed that allicin reduced PA-induced lipid accumulation using Nile red staining and TC and TG assays. Then, 219 potential targets of allicin were successfully predicted by PharmMapper. According to Reactome Pathway Analysis, 44 potential targets related to lipid metabolism were screened out. Molecular signaling cascades mediated by allicin included PPARA, PPARG, FABP4, and FABP6 by cytoHubba and qPCR analysis. Results revealed that allicin activated the gene expression of PPARA and FABP6 and suppressed the gene expression of FABP4 and PPARG. Thus, the present study united the methods of network pharmacology and experimental validation to investigate the protein targets of allicin on PA-induced lipid metabolism disorders to supply a reference for related application for the first time.

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