Oleic Acid-induced Lipid Accumulation Research Articles

Exploring the Putative Involvement of MALAT1 in Mediating the Beneficial Effect of Exendin-4 on Oleic Acid-Induced Lipid Accumulation in HepG2 Cells

Background/Objectives: The reduction of oleic acid (OA)-induced steatosis in HepG2 cells observed upon treatment with the glucagon-like peptide-1 receptor agonist (GLP-1RA) Exendin-4 (Ex-4) is associated with the modulation of the expression of several microRNAs, long non-coding RNAs (lncRNAs), and mRNAs. Notably, MALAT1, an lncRNA, shows significant downregulation in the presence of Ex-4 as compared to OA alone. In this study, we aimed to explore the role of MALAT1 in the positive impact of Ex-4 on OA-induced lipid accumulation in HepG2 cells. Methods: Steatosis in HepG2 cells was induced by treating them with 400 µM OA. The effect of Ex-4 on steatosis was examined by treating the steatotic cells with 200 nM of EX-4 for 3 h. MALAT1 was silenced with siRNA, while gene expression was quantified using qRT-PCR. Results: In the presence of Ex-4, the silencing of MALAT1 did not exert any discernible influence on de novo lipogenesis genes such as PPARγ and SREBP1. However, MALAT1 silencing significantly affected, to varying degrees, the expression levels of several lipid metabolism genes such as FAS, ACADL, CPT1A, and MTTP. Conclusions: Further investigations are warranted to fully decipher the role of the Ex-4-MALAT1 in the positive impact of GLP-1RAs on steatosis.

Polyoxometalates Ameliorate Metabolic Dysfunction-Associated Steatotic Liver Disease by Activating the AMPK Signaling Pathway.

Metabolic dysfunction-associated steatotic liver disease (MASLD), the most prevalent chronic liver disorder, has garnered increasing attention globally owing to its associated health complications. However, the lack of available therapeutic medications and inadequate management of complications in metabolic dysfunction-associated steatohepatitis (MASH) present significant challenges. There are little studies evaluating the effectiveness of POM in treating MASLD. In this study, we synthesized polyoxometalates (POM) for potential treatment of MASLD. We induced liver disease in mice using two approaches: feeding a high-fat diet (HFD) to establish MASLD or feeding a methionine-choline deficient (MCD) diet to induce hepatic lipotoxicity and MASH. Various metabolic parameters were detected, and biochemical and histological evaluations were conducted on MASLD. Western blotting, qRT-PCR and immunofluorescence assays were used to elucidate the molecular mechanism of POM in the treatment of MASLD. POM therapy resulted in significant improvements in weight gain, dyslipidemia, liver injury, and hepatic steatosis in mice fed a HFD. Notably, in a more severe dietary-induced MASH model with MCD diet, POM significantly attenuated hepatic lipid accumulation, inflammation, and fibrosis. POM treatment effectively attenuated palmitic acid and oleic acid-induced lipid accumulation in HepG2 and Huh7 cells by targeting the AMPK pathway to regulate lipid metabolism, which was confirmed by AMPK inhibitor. Additionally, the activation of AMPK signaling by POM suppressed the expression of lipid synthesis genes, including sterol regulatory element-binding protein 1c (SREBP1c) and SREBP2, while concurrently upregulating the expression of sirtuin 1 (SIRT1) to promote fatty acid oxidation. These findings suggest that POM is a promising therapeutic strategy with high efficacy in multiple MASLD models.

Ultra-high pressure assisted extraction of polysaccharide from Bangia fusco-purpurea: Structure and in vitro hypolipidemic activity

The structure and in vitro hypolipidemic activity of Bangia fusco-purpurea polysaccharide (BFP) assisted extracted with ultra-high pressure (UHP) at 100-600MPa were studied. Compared to native BFP, UHP assisted extracted BFP had a more loose network structure with higher total sugar and uronic acid contents while less molecular weight (p<0.05). Moreover, UHP assisted extraction significantly improved the in vitro hypolipidemic and antioxidant activity of BFP. Especially at 400MPa UHP, the cholesterol adsorption and antioxidant capacities of BFP were increased by approximately 38.02% and 11.69%-32.29%, respectively. BFP with UHP assisted extraction could alleviate oleic acid-induced lipid accumulation and lipid oxidation in HepG2 cells more effectively by activating the AMPK signaling pathway as well as inhibiting PPARγ expression, which was much related with its reduced molecular weight and loose network structure. The findings indicated that UHP assisted extracted BFP has better potential to develop natural hypolipidemic agent.

Dendrobine alleviates oleic acid-induced lipid accumulation by inhibiting FOS/METTL14 pathway.

Dendrobine (DDB), an alkaloid isolated from the Chinese herb Dendrobium, has antioxidant and anti-inflammatory effects; however, whether DDB reduces oleic acid (OA)-induced lipid accumulation remains unclear. OA-induced lipid accumulation model of HepG2 cells were treated with DDB. Cellular lipid deposition was assessed by Oil Red O (ORO) staining and triglyceride and total cholesterol detection. RNA-Sequencing (RNA-seq), biological function analysis, and transcription factor (TFs) prediction were combined to identify key TF in the DDB-treated OA model. Finally, the roles of FOS and METTL14 were examined using a DDB-induced lipid accumulation model. DDB inhibited OA-induced lipid accumulation. We identified 895 differentially expressed genes (DEGs) that were mainly enriched in various biological processes of lipid synthesis and transport. Four transcription factors (SOX9, MLXIPL, FOS, and JUN) associated with lipid metabolism and FOS levels in the OA-induced lipid accumulation model after DDB treatment had the greatest changes in expression change. Overexpression of FOS alleviates the inhibitory effect of DDB on OA-induced lipid accumulation. METTL14 is a target gene of FOS, and simultaneous interference with METTL14 in cells with high FOS expression restored the alleviating effect of DDB on lipid accumulation. DDB alleviated OA-induced lipid accumulation by inhibiting the FOS/METTL14 pathway.

Tartaric acid ameliorates experimental non-alcoholic fatty liver disease by activating the AMP-activated protein kinase signaling pathway

Tartaric acid (TA) has been shown beneficial effects on blood pressure and lipid levels. However, its effect on non-alcoholic fatty liver disease (NAFLD) remains unknown. This study aimed to investigate the role of TA in experimental NAFLD. Mice were fed a Western diet for 8 weeks, followed by administration of TA or a vehicle for an additional 12 weeks while continuing on the Western diet. Blood biochemistry including transaminases and glucose tolerance test and liver tissue RNA sequencing (RNA-seq), lipid content, and histology were investigated. The HepG2 cell line was used to explore the mechanism by which TA regulates lipid metabolism. We found that TA significantly improved weight gain, insulin resistance, hepatic steatosis, inflammation and fibrosis in Western diet-fed mice. By comparing gene expression differences, we found that TA affects pathways related to lipid metabolism, inflammatory response, and fibrosis. Furthermore, TA effectively reduced oleic acid-induced lipid accumulation in HepG2 cells and downregulated the genes associated with fatty acid synthesis, which were enriched in the AMP-activated protein kinase (AMPK) signaling pathway. TA also enhanced the phosphorylation of AMPK which could be reverted by the AMPK inhibitor Compound C in HepG2 cells. Our study suggests that TA improves experimental NAFLD by activating the AMPK signaling pathway. These findings indicate that TA may serve as a potential therapy for the human NAFLD.

Analysis of the therapeutic potential of miR-124 and miR-16 in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a common condition affecting >25% of the population worldwide. This disorder ranges in severity from simple steatosis (fat accumulation) to severe steatohepatitis (inflammation), fibrosis and, at its end-stage, liver cancer. A number of studies have identified overexpression of several key genes that are critical in the initiation and progression of NAFLD. MiRNAs are potential therapeutic agents that can regulate several genes simultaneously. Therefore, we transfected cell lines with two key miRNAs involved in targeting NAFLD-related genes. The suppression effects of the investigated miRNAs (miR-124 and miR-16) and genes (TNF, TLR4, SCD, FASN, SREBF2, and TGFβ-1) from our previous study were investigated by real-time PCR in Huh7 and HepG2 cells treated with oleic acid. Oil red O staining and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay were utilized to assess cell lipid accumulation and cytotoxic effects of the miRNAs, respectively. The pro-oxidant-antioxidant balance (PAB) assay was undertaken for miR-16 and miR-124 after cell transfection. Following transfection of miRNAs into HepG2, oil red O staining showed miR-124 and miR-16 reduced oleic acid-induced lipid accumulation by 35.2% and 28.6% respectively (p<0.05). In Huh7, miR-124 and miR-16 reduced accumulation by 23.5% and 31.3% respectively (p<0.05) but without impacting anti-oxidant activity. Real-time PCR in HepG2 revealed miR-124 decreased expression of TNF by 0.13-fold, TLR4 by 0.12-fold and SREBF2 by 0.127-fold (p<0.05). miR-16 decreased TLR4 by 0.66-fold and FASN by 0.3-fold (p<0.05). In Huh7, miR-124 decreased TNF by 0.12-fold and FASN by 0.09-fold (p<0.05). miR-16 decreased SCD by 0.28-fold and FASN by 0.64-fold (p<0.05). MTT assays showed, in HepG2, viability was decreased 24.7% by miR-124 and decreased 33% by miR-16 at 72h (p<0.05). In Huh7, miR-124 decreased viability 42% at 48h and 29.33% at 72h (p<0.05), while miR-16 decreased viability by 32.3% (p<0.05). These results demonstrate the ability of miR-124 and miR-16 to significantly reduce lipid accumulation and expression of key pathogenic genes associated with NAFLD through direct targeting. Though this requires further in vivo investigation.

Screening of fish oil fatty acids for antihyperlipidemic activity based on network pharmacology and validation of synergistic efficacy in vitro

Screening of fish oil fatty acids for antihyperlipidemic activity based on network pharmacology and validation of synergistic efficacy in vitro

Structure and activity of new degraded products of limonoid from root bark of Dictamnus dasycarpus, and insights from broadened NMR spectra into self-aggregation of hydroxy acids

Structure and activity of new degraded products of limonoid from root bark of Dictamnus dasycarpus, and insights from broadened NMR spectra into self-aggregation of hydroxy acids

The Peptide AWRK6 Alleviates Lipid Accumulation in Hepatocytes by Inhibiting miR-5100 Targeting G6PC.

Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease, with a worldwide prevalence of more than 25%, and there is no approved drug for NAFLD specifically. In our previous study, the synthetic peptide AWRK6 was found to ameliorate NAFLD in mice. However, the mechanisms involved are still largely unknown. Here, AWRK6 treatment presented an alleviative effect on lipid accumulation induced by oleic acid in hepatocytes. Meanwhile, miR-5100 and miR-505 were found to be elevated by oleic acid induction and reversed by AWRK6 incubation. Further, the miR-5100 inhibitor inhibited oleic acid-induced lipid accumulation, and the alleviation effect of AWRK6 was partially counteracted by miR-5100 mimics. The screening of potential target genes revealed that a catalytic subunit of G6Pase G6PC was significantly inhibited by miR-5100 mimics transfection in both mRNA and protein levels. The direct targeting of miR-5100 on G6PC was verified by a Dual-Luciferase Reporter Assay. Moreover, the mRNA and protein levels of G6PC were found to be significantly increased by AWRK6 treatment. These results suggested that the peptide AWRK6 could alleviate lipid accumulation in hepatocytes, partly through reducing miR-5100 to restore one of its targets: G6PC. Thus, AWRK6 has the potential to treat NAFLD. Additionally, miR-5100 is a mediator of lipid accumulation in hepatocytes, which could be targeted by AWRK6.

ATG5-Mediated Autophagy May Inhibit Pyroptosis to Ameliorate Oleic Acid-Induced Hepatocyte Steatosis.

Despite activated autophagy ameliorating hepatocyte steatosis and metabolic associated fatty liver disease (MAFLD), mechanisms underlying the beneficial roles of autophagy in hepatic deregulation of lipid metabolism remain undefined. We explored whether autophagy can ameliorate oleic acid (OA)-induced hepatic steatosis by suppressing pyroptosis. Pyroptosis is involved in hepatocyte steatosis induced by OA. In addition, autophagy flux was blocked in OA-treated hepatocytes. Treatment with OA induced lipid accumulation in liver cell line L-02, which was attenuated by rapamycin (Rap), an autophagy agonist, while aggravated by autophagy inhibitor bafilomycin A1 (Baf A1). Inversely, treatment with pyroptotic agonist Nigericin aggravated OA-induced hepatic steatosis, while pyroptosis antagonist disulfiram ameliorated this effect. Mechanistically, treatment with Rap downregulated the expression of pyroptosis-related proteins, including NLRP3, Caspase-1, IL-18, GSDMD expression evoked by OA, thus improving pyroptosis in hepatic steatosis. Significantly, overexpression of ATG5 obviously downregulated cleaved caspase-1 expressions without altering the total caspase1 expressions in hepatic cell steatosis. Taken together, our studies strongly demonstrated that the activation of ATG5 inhibits pyroptosis to improve hepatic steatosis and suggest autophagy activation as a potential therapeutic strategy for pyroptosis-mediated MAFLD.

BCATc inhibitor 2 ameliorated mitochondrial dysfunction and apoptosis in oleic acid-induced non-alcoholic fatty liver disease model.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent hepatic disease in the world. Disorders of branched chain amino acid (BCAA) metabolism is involved in various diseases. In this study, we aim to explore the role of BCAA metabolism in the development of NAFLD and the protective effect of BCATc Inhibitor 2, an inhibitor of cytosolic branched chain amino acid transaminase, against NAFLD as well as its underlying mechanism. It was found that oleic acid induced lipid accumulation and apoptosis in HepG2 and LO2 cells. Supplementation of BCAAs further aggravated oleic acid-induced lipid accumulation and apoptosis. In contrast, treatment of BCATc Inhibitor 2 ameliorated oleic acid-induced lipid accumulation and apoptosis. Molecularly, supplementation of BCAAs or treatment of BCATc Inhibitor 2 up-regulated or down-regulated the expression of SREBP1 and lipogenesis-related genes without affecting lipolysis-related genes. BCATc Inhibitor 2 maintained mitochondrial function by ameliorating oleic acid-induced mitochondrial ROS generation and mitochondrial membrane potential disruption. In addition, BCATc Inhibitor 2 treatment alleviated oleic acid-induced activation of JNK and AKT signaling pathway and Bcl2/Bax/Caspase axis. In conclusion, our results indicate BCAA metabolism is involved in NAFLD and BCATc Inhibitor 2 protects against oleic acid-induced lipid accumulation and apoptosis. These findings suggest that BCATc Inhibitor 2 is a promising candidate drug for the treatment of NAFLD.

Dihydroflavonoid glycosides from Viscum album and their inhibitory effects on hepatic lipid accumulation and target identification

Five undescribed dihydroflavonoid glycoside derivatives, namely albvisosides A‒E, together with two known compounds were isolated from the roots and stem leaves of Viscum album L. var. album. (European mistletoe). Their structures were determined by HRESIMS, 1D and 2D NMR, and ECD analysis. Albvisoside B exhibits significant inhibitory effect on hepatic lipid accumulation in HepG2 cells at very low concentrations (EC50: 0.7nM). Using proteome integral solubility alteration assay, the direct targets or downstream effectors of albvisoside B were elucidated. As a result, 97 proteins were identified based on ligand-induced alterations in the protein thermal stability. Bioinformatics analysis indicated that albvisoside B primarily ameliorated oleic acid-induced lipid accumulation by regulating the selenoamino acids metabolism signaling pathway. RPL3, ADAM17, and RPL14 were likely to be involved in mediating the lipid-lowering effect of albvisoside B.

Bifendate inhibits autophagy at multiple steps and attenuates oleic acid-induced lipid accumulation

Some traditional Chinese medicines exert roles in the therapy of liver diseases by modulating autophagy. Bifendate (DDB), a synthetic intermediate of Schisandrin C extracted from Schisandrae chinensis, is clinically used to treat hepatitis in China. While DDB is a positive control to research some potential hepatoprotective agents, its related molecular mechanisms are unknown. In this study, we show that DDB inhibited autophagosome-lysosome fusion, lysosome acidification and autophagic lysosome reformation. Moreover, DDB attenuated oleic acid-induced lipid droplet accumulation. These findings reveal the effects of DDB on the autophagy-related processes and lysosomal function, and also provide a possibility to understand the bioactivity mechanism of DDB in the future.

Mulberry Leaf Extract Improves Metabolic Syndrome by Alleviating Lipid Accumulation In Vitro and In Vivo.

Metabolic syndrome (MS) is a metabolic disease with multiple complications. Mulberry leaf extract (MLE) is rich in flavonoids and has great potential in alleviating glucose and lipid metabolism disorders. This study evaluated the effect and mechanism of MLE on the alleviation of MS. The components of the MLE were analyzed, and then the regulation of lipid metabolism by MLE in vitro and in vivo was determined. In a hepatocyte model of oleic acid-induced lipid accumulation, it was found that MLE alleviated lipid accumulation and decreased the expression of genes involved in lipogenesis. Furthermore, MLE improved obesity, insulin resistance, plasma lipid profile, and liver function in MS mice after a 15-week intervention. MLE decreased the expression of SREBP1, ACC, and FAS through the AMPK signaling pathway to inhibit lipid synthesis and increase the level of CPT1A to promote lipid decomposition to achieve its hypolipidemic effect. Meanwhile, MLE was also shown to affect the composition of the gut microbiota and the production of short-chain fatty acids, which contributed to the alleviation of lipid accumulation. Our results suggest that MLE can improve MS by improving lipid metabolism through multiple mechanisms and can be developed into dietary supplements for the improvement of MS.

Acacetin Protects against Non-Alcoholic Fatty Liver Disease by Regulating Lipid Accumulation and Inflammation in Mice.

We previously demonstrated that acacetin reduces adipogenesis in adipocytes, and decreases lipid accumulation in visceral adipocyte tissue. Here we investigated whether acacetin regulated the mechanisms of lipogenesis and inflammation in non-alcoholic fatty liver disease (NAFLD) in obese mice. Male C57BL/6 mice were fed a high-fat diet (HFD), and then administered acacetin by intraperitoneal injection. Acacetin reduced body weight and liver weight in obese mice. Acacetin-treated obese mice exhibited decreased lipid accumulation, increased glycogen accumulation, and improved hepatocyte steatosis. Acacetin regulated triglycerides and total cholesterol in the liver and serum. Acacetin decreased low-density lipoprotein and leptin concentrations, but increased high-density lipoprotein and adiponectin levels in obese mice. Acacetin effectively weakened the gene expressions of transcription factors related to lipogenesis, and promoted the expressions of genes related to lipolysis and fatty acid β-oxidation in liver. Acacetin also reduced expressions of inflammation-related cytokines in the serum and liver. Oleic acid induced lipid accumulation in murine FL83B hepatocytes, and the effects of acacetin treatment indicated that acacetin may regulate lipid metabolism through the AMPK pathway. Acacetin may protect against hepatic steatosis by modulating inflammation and AMPK expression.

Silymarin diminishes oleic acid-induced lipid accumulation in HepG2 cells by modulating the expression of endoplasmic reticulum stress markers

Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder which presents with the accumulation of triglycerides in hepatocytes due to imbalances in the uptake, synthesis, export, and oxidation of fatty acids. Silymarin is a flavonolignan derived from milk thistle, a herbal medicine that has been used for centuries to treat liver disease. In this study, the effect of silymarin on genes involved in lipogenesis and endoplasmic reticulum (ER) stress was investigated in the cellular NAFLD model. HepG2 cells were treated with 0.5 mM oleic acid (OA) in the presence or absence of silymarin for 24 h, and subsequently, lipid accumulation was assessed by staining the cells with Oil red O as well as the measurement of intracellular triglyceride (TG) content with an enzymatic method. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used to measure the expression of sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), Sirtuin 1 (SIRT1), TRB3, and ATF4. Lipid accumulation was increased in OA-treated hepatocytes, an effect that was attenuated by silymarin. The expression of FAS, SREBP-1, TRB3, and ATF4 was significantly increased in OA-treated HepG2 cells, while the expression of SIRT1 was decreased. Treatment with silymarin could successfully diminish SREBP-1, FAS, TRB3, and ATF4 gene expression while augmenting the expression of SIRT1. Silymarin not only efficiently reduces lipogenesis but also decreases ER stress, which is a critical parameter in lipogenesis. Therefore, silymarin might be considered an effective supplementary option in the treatment of liver steatosis.

A Strategy for Screening the Lipid-Lowering Components in Alismatis Rhizoma Decoction Based on Spectrum-Effect Analysis.

Alismatis Rhizoma decoction (ARD), comprised of Alisma plantago-aquatica subsp. orientale (Sam.) Sam and Atractylodes macrocephala Koidz. at a ratio of 5 : 2, is a classic traditional Chinese medicine (TCM) formula with successful clinical hypolipidemic effect. This paper aimed to explore the major bioactive compounds and potential mechanism of ARD in the treatment of hyperlipidemia on the basis of spectrum-effect analysis and molecular docking. Nine ARD samples with varying ratios of the constituent herbs were prepared and analyzed by UPLC-Q-TOF/MS to obtain the chemical spectra. Then, the lipid-lowering ability of the nine samples was tested in an oleic acid-induced lipid accumulation model in human hepatoma cells (HepG2). Grey relational analysis and partial least squares regression analysis were then performed to determine the correlation between the chemical spectrums and lipid-lowering efficacies of ARD. The potential mechanisms of the effective compounds were investigated by docking with the farnesoid X receptor (FXR) protein. The results indicated that alisol B 23-acetate, alisol C 23-acetate, and alisol B appeared to be the core effective components on hyperlipidemia in ARD. Molecular docking further demonstrated that all three compounds could bind to FXR and were potential FXR agonists for the treatment of hyperlipidemia. This study elucidated the effective components and potential molecular mechanism of action of ARD for treating hyperlipidemia from a perspective of different compatibility, providing a new and feasible reference for the research of TCM formulas such as ARD.

Capsaicin Attenuates Oleic Acid-Induced Lipid Accumulation via the Regulation of Circadian Clock Genes in HepG2 Cells.

As the major component in red chili peppers, capsaicin is useful in the prevention of lipid metabolism disorders. In this study, the attenuation effect of capsaicin on oleic acid (OA)-induced lipid accumulation in HepG2 cells was evaluated with respect to circadian clock gene expressions. Lipid profiles, including triacylglycerols, total cholesterols, high-density lipoproteins, low-density lipoproteins, and aspartate aminotransferase content, were measured using enzymatic assay kits. The mitochondrial membrane potential, cellular redox status, and lipid droplet morphology were also determined using different assay kits and staining methods. The mRNA and protein expressions of core circadian clock genes and major lipometabolism-related factors were assessed using RT-qPCR and western blotting. Results showed that 50 μM capsaicin alleviated the circadian desynchrony and inhibited OA-induced ROS overproduction (from 166.44 ± 12.63% to 119.90 ± 5.43%) and mitochondrial dysfunction (from 0.60 ± 0.08 to 0.83 ± 0.09, represented by the red/green fluorescence ratio) in HepG2 cells. The amelioration effect of capsaicin on OA-induced lipid accumulation was weakened after Bmal1-knockdown, demonstrating that the rhythmic expression of the circadian clock gene is involved in the regulation process of capsaicin in lipid metabolism.

(+)-Dehydrovomifoliol Alleviates Oleic Acid-Induced Lipid Accumulation in HepG2 Cells via the PPARα-FGF21 Pathway.

An overload of hepatic fatty acids, such as oleic acid is a key trigger of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether Artemisia frigida, a valuable traditional medicine used to treat various diseases, could mitigate OA-induced lipid accumulation in HepG2 cells. Then, to identify the active substances in A. frigida, a phytochemistry investigation was conducted using a bioassay-guided isolation method. Consequently, one terpene (1) and one flavone (2) were identified. Compound 1 ((+)-dehydrovomifoliol) exhibited potent effects against lipid accumulation in OA-induced HepG2 cells, without causing cyto-toxicity. Notably, treatment with (+)-dehydrovomifoliol decreased the expression levels of three genes related to lipogenesis (SREBP1, ACC, and FASN) and increased those of three genes related to fatty acid oxidation (PPARα, ACOX1, and FGF21). In addition, similar results were observed for SREBP1, PPARα, and FGF21 protein levels. The effects of (+)-dehydrovomifoliol were partially reversed by treatment with the PPARα antagonist GW6471, indicating the important role of the PPARα–FGF21 axis in the effects of (+)-dehydrovomifoliol. Based on its effects on hepatic lipogenesis and fatty acid oxidation signaling via the PPARα–FGF21 axis, (+)-dehydrovomifoliol isolated from A. frigida could be a useful early lead compound for developing new drugs for NAFLD prevention.

SREBP1c silencing reduces endoplasmic reticulum stress and related apoptosis in oleic acid induced lipid accumulation

Objective: Sterol regulatory element binding protein 1c (SREBP1c) is one of the major transcription factors that is involved in nonalcoholicfatty liver disease (NAFLD) development by increasing hepatic fatty acid and triglyceride synthesis. Our study aimed toinvestigate the interaction of SREBP1c with endoplasmic reticulum (ER) stress in oleic acid (OA) induced lipid accumulation.Material and Methods: Optimum lipid droplet (LD) formation and SREBP-1c induction were determined in alpha mouse liver12 (AML12) hepatocytes following the incubation with different OA concentrations. To determine the effect of SREBP-1c, cellswere transfected with siRNA specific for SREBP-1c. LD formation and SREBP-1c induction were determined via Oil Red O andimmunblotting, respectively. Phospho IRE1, GRP78, CHOP, ATF6 and JNK levels were determined with immunofluorescencestaining.Results: Optimum LD formation and SREBP-1c induction were achieved at 0.5 mM oleat concentration. While SREBP-1c silencingdecreased LD formation in non-OA treated cells, no significant effect of silencing was determined following OA administration. Onthe other hand, SREBP-1c silencing in OA treated cells reduced phospho IRE1, ATF6, JNK and CHOP expressions.Conclusion: Our results suggest that the novel function of SREBP-1c can regulate ER stress response in OA induced lipid accumulation.