Ethyl 2,4,6-trihydroxybenzoate is an agonistic ligand for liver X receptor that induces cholesterol efflux from macrophages without affecting lipid accumulation in HepG2 cells

2012 ◽  
Vol 22 (12) ◽  
pp. 4094-4099 ◽  
Author(s):  
Minh-Hien Hoang ◽  
Yaoyao Jia ◽  
Hee-jin Jun ◽  
Ji-Hae Lee ◽  
Dong-Ho Lee ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Cholesterol Efflux ◽  
Liver X Receptor

scholarly journals Pharmacological activation of liver X receptor during cigarette smoke exposure adversely affects alveolar macrophages and pulmonary surfactant homeostasis

2019 ◽  
Vol 316 (4) ◽  
pp. L669-L678 ◽  
Author(s):  
Éric Jubinville ◽  
Joanie Routhier ◽  
Michaël Maranda-Robitaille ◽  
Marie Pineault ◽  
Nadia Milad ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Alveolar Macrophages ◽  
Lipid Accumulation ◽  
Pulmonary Surfactant ◽  
Cholesterol Efflux ◽  
Liver X Receptor ◽  
Smoke Exposure ◽  
Lipid Transport ◽  
Cigarette Smoke Exposure ◽  
Cholesterol Efflux Capacity

Smoking alters pulmonary reverse lipid transport and leads to intracellular lipid accumulation in alveolar macrophages. We investigated whether stimulating reverse lipid transport with an agonist of the liver X receptor (LXR) would help alveolar macrophages limit lipid accumulation and dampen lung inflammation in response to cigarette smoke. Mice were exposed to cigarette smoke and treated intraperitoneally with the LXR agonist T0901317. Expression of lipid capture and lipid export genes was assessed in lung tissue and alveolar macrophages. Pulmonary inflammation was assessed in the bronchoalveolar lavage (BAL). Finally, cholesterol efflux capacity and pulmonary surfactant levels were determined. In room air-exposed mice, T0901317 increased the expression of lipid export genes in macrophages and the whole lung and increased cholesterol efflux capacity without inducing inflammation or affecting the pulmonary surfactant. However, cigarette smoke-exposed mice treated with T0901317 showed a marked increase in BAL neutrophils, IL-1α, C-C motif chemokine ligand 2, and granulocyte-colony-stimulating factor levels. T0901317 treatment in cigarette smoke-exposed mice failed to increase the ability of alveolar macrophages to export cholesterol and markedly exacerbated IL-1α release. Finally, T0901317 led to pulmonary surfactant depletion only in cigarette smoke-exposed mice. This study shows that hyperactivation of LXR and the associated lipid capture/export mechanisms only have minor pulmonary effects on the normal lung. However, in the context of cigarette smoke exposure, where the pulmonary surfactant is constantly oxidized, hyperactivation of LXR has dramatic adverse effects, once again showing the central role of lipid homeostasis in the pulmonary response to cigarette smoke exposure.

Anti-obesity Effect of Gold Nanoparticles from Dendropanax morbifera Léveille by Suppression of Triglyceride Synthesis and Downregulation of PPARγ and CEBPα Signaling Pathways in 3T3-L1 Mature Adipocytes and HepG2 Cells

2020 ◽  
Vol 16 (2) ◽  
pp. 196-203 ◽  
Author(s):  
Myoung Hi Yi ◽  
Shakina Yesmin Simu ◽  
Sungeun Ahn ◽  
Verónica Castro Aceituno ◽  
Chao Wang ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Cellular Level ◽  
Dendropanax Morbifera ◽  
Immunoblotting Assay ◽  
Triglyceride Content ◽  
20 Nm ◽  
Proliferation Assays

Background: Biosynthesis of gold nanoparticles from medicinal plants has become an interesting strategy in biomedical research due to its exclusive properties including less toxic cellular level through its ecofriendly biological function. Objective: To examine the anti-lipid accumulation effect of spherical gold nanoparticles (size 10-20 nm) synthesized from Dendropanax morbifera Léveille (D-AuNPs) in both 3T3-L1 and HepG2 cells. Method: 3T3-L1 preadipocytes and HepG2 hepatocytes were stimulated with cocktail media to generate obese and fatty liver disease models. Cell cytotoxicity and cell proliferation assays were performed in adipocytes at different stages of growth. An anti-lipid accumulation assay was performed in 3T3-L1 obese and HepG2 fatty liver models using different doses of D-AuNPs. Expression of adipogenic genes of PPARγ, CEBPα, Jak2, STAT3, and ap2 and hepatogenic genes PPARα, FAS, and ACC was measured by real-time PCR. In addition, protein expression of PPARγ and CEBPα was evaluated by immunoblotting assay. Result: We found that D-AuNPs (size 10–20 nm) at concentrations up to 100 µg/ml were nontoxic to 3T3-L1 and HepG2 at post-confluent and mature stages. In addition, pretreatment of D-AuNPs at post-confluent stage reduced triglyceride content. In addition, the adipogenesis process was negatively controlled by D-AuNPs, with downregulated PPARγ, CEBPα, Jak2, STAT3, and ap2 expression in 3T3-L1 cells and FAS and ACC levels in HepG2 cells. Conclusion: These data indicated that D-AuNPs exert antiadipogenic properties. We hypothesize that Dendropanax contains a large amount of phenolic compound that coats the surface of gold nanoparticles and has the ability to reduce the excess amount of lipid in both cell lines.

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.

Unsaponifiable Matter from Rice Bran Attenuates High Glucose-Induced Lipid Accumulation by Activating AMPK in HepG2 Cells

2016 ◽  
Vol 41 (2) ◽  
pp. e12313
Author(s):  
Hyeonmi Ham ◽  
Koan Sik Woo ◽  
Yu Young Lee ◽  
Byongwon Lee ◽  
In-Hwan Kim ◽  
...  
Keyword(s):  
Unsaponifiable Matter ◽  
Rice Bran ◽  
High Glucose ◽  
Lipid Accumulation ◽  
Hepg2 Cells

scholarly journals Kaempferol and Kaempferide Attenuate Oleic Acid-Induced Lipid Accumulation and Oxidative Stress in HepG2 Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8847
Author(s):  
Fangfang Tie ◽  
Jin Ding ◽  
Na Hu ◽  
Qi Dong ◽  
Zhi Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Oleic Acid ◽  
Lipid Metabolism ◽  
Western Blot ◽  
Blot Analysis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Western Blot Analysis ◽  
Heme Oxygenase 1 ◽  
And Oxidative Stress

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases which lacks ideal treatment options. Kaempferol and kaempferide, two natural flavonol compounds isolated from Hippophae rhamnoides L., were reported to exhibit a strong regulatory effect on lipid metabolism, for which the mechanism is largely unknown. In the present study, we investigated the effects of kaempferol and kaempferide on oleic acid (OA)-treated HepG2 cells, a widely used in vitro model of NAFLD. The results indicated an increased accumulation of lipid droplets and triacylglycerol (TG) by OA, which was attenuated by kaempferol and kaempferide (5, 10 and 20 μM). Western blot analysis demonstrated that kaempferol and kaempferide reduced expression of lipogenesis-related proteins, including sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD-1). Expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding proteins β (C/EBPβ), two adipogenic transcription factors, was also decreased by kaempferol and kaempferide treatment. In addition, western blot analysis also demonstrated that kaempferol and kaempferide reduced expression of heme oxygenase-1 (HO-1) and nuclear transcription factor-erythroid 2-related factor 2 (Nrf2). Molecular docking was performed to identify the direct molecular targets of kaempferol and kaempferide, and their binding to SCD-1, a critical regulator in lipid metabolism, was revealed. Taken together, our findings demonstrate that kaempferol and kaempferide could attenuate OA-induced lipid accumulation and oxidative stress in HepG2 cells, which might benefit the treatment of NAFLD.

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