Corrigendum to "Zanthoxylum ailanthoides Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells".
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ABSTRACT:
SUBMITTER: Kwon EB
PROVIDER: S-EPMC6662453 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Corrigendum to "<i>Zanthoxylum ailanthoides</i> Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells".
Kwon Eun-Bin EB Kang Myung-Ji MJ Kim Soo-Yeon SY Lee Yong-Moon YM Lee Mi-Kyeong MK Yuk Heung Joo HJ Ryu Hyung Won HW Lee Su Ui SU Oh Sei-Ryang SR Moon Dong-Oh DO Lee Hyun-Sun HS Kim Mun-Ock MO
Evidence-based complementary and alternative medicine : eCAM 20190714
[This corrects the article DOI: 10.1155/2018/3140267.]. ...[more]
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Project description:Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-?, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells.
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Project description: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.
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Project description:Delphinidin is an anthocyanidin commonly found in various fruits and vegetables. Delphinidin has been known to possess many functions, such as an antioxidant, and anti-inflammatory, anti-cancer and anti-muscular atrophy agent. In this study, we attempted to evaluate the effects of delphinidin on lipid accumulation in hepatocytes. The results showed that palmitic acid (PA)-induced cellular senescence in HepG2 cells and reduced the expression of SMARCD1, which is known to regulate senescence-associated lipid accumulation in hepatocytes. However, delphinidin-3-glucoside (D3 g) suppressed PA-induced senescence and reversed the expression of SMARCD1 to the level of untreated HepG2 cells. Consequently, D3 g inhibited PA-induced lipid accumulation through the restoration of the expression of SMARCD1 and fatty acid oxidation genes. Taken together, our results suggest that D3 g suppresses the lipid accumulation induced by hepatocyte senescence.
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Project description: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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Project description:Sesamin, a special compound present in sesame and sesame oil, has been reported the role in regulating blood lipids and improving liver function, while the underlying mechanisms remain unclear. This study aims to explore its potential mechanisms in regulating lipid metabolism. HepG2 cells were treated with oleic acid to establish an in vitro high-fat cell model to simulate impaired hepatocytes under lipid metabolism disorders.Differentially expressed genes during the sesame intervention were screened by RNA sequencing (RNA seq) and validated using real-time quantitative PCR and Western blot.The data showed that sesamin significantly upregulated the mRNA levels of genes involved in fatty acid metabolism processes such as ETFB, ACAT2, FADS2, FABP1, ACOT1, and those involved in cholesterol metabolism processes such as FDPS, PCSK9, and DHCR7, and downregulated the mRNA levels of CYP24A1 and GGT5 involved in fatty acid metabolism, as well as MVK involved in cholesterol synthesis. Sesamin significantly down-regulated the protein levels of NOTCH1, CD36, SOX4, and FABP1. In summary, sesamin alleviates lipid accumulation in HepG2 by regulating lipid metabolism, with potential mechanisms involving steroid biosynthesis, unsaturated fatty acid biosynthesis, fat digestion and absorption, fatty acid metabolism, Notch signaling pathway, and PPAR signaling pathway.
2023-12-05 | GSE248903 | GEO
Project description:Rationale: Acute kidney injury (AKI) is a serious clinical emergency with an acute onset, rapid progression, and poor prognosis. Recent evidence suggests that AKI is accompanied by significant metabolic abnormalities, including alterations in lipid metabolism. However, the specific changes in lipids in AKI, and their role and regulation mechanisms are currently unclear. Methods: Quantitative metabolomics was performed in AKI models to reveal the differences of lipid metabolism-related products. Regulated pathway was detected by western blot, qRT-PCR, immunoblot analysis and immunohistochemistry. Results: The present study systematically analyzes the changes in lipid composition in AKI for the first time and find that the degree of lipid accumulation was highly correlated with uncoupling protein 1 (UCP1). Importantly, relieving lipid accumulation in AKI by upregulating UCP1 can significantly inhibit the progression of AKI through promoting AMPK/ULK1/autophagy pathway. Conclusions: The present findings suggest that lipid accumulation in AKI is directly regulated by UCP1, which can activate cell autophagy and thus significantly inhibit disease progression. It will provide new ideas and targets for the treatment of AKI.
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Project description:Lipid metabolism is important for health and insulin action, yet the fundamental process of regulating lipid metabolism during muscle contraction is incompletely understood. Here, we show that liver kinase B1 (LKB1) muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation during treadmill exercise. LKB1 MKO mice also show decreased muscle SIK3 activity, increased histone deacetylase 4 expression, decreased NAD? concentration and SIRT1 activity, and decreased expression of genes involved in FA oxidation. In AMP-activated protein kinase (AMPK)?2 KO mice, substrate use was similar to that in WT mice, which excluded that decreased FA oxidation in LKB1 MKO mice was due to decreased AMPK?2 activity. Additionally, LKB1 MKO muscle demonstrated decreased FA oxidation in vitro. A markedly decreased phosphorylation of TBC1D1, a proposed regulator of FA transport, and a low CoA content could contribute to the low FA oxidation in LKB1 MKO. LKB1 deficiency did not reduce muscle glucose uptake or oxidation during exercise in vivo, excluding a general impairment of substrate use during exercise in LKB1 MKO mice. Our findings demonstrate that LKB1 is a novel molecular regulator of major importance for FA oxidation but not glucose uptake in muscle during exercise.
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Project description:Methods: We performed mRNA sequence analysis by deep sequencing, in triplicate, using Illumina HiSeq to assess the impact of PHLPP1 knockdown in regulating gene expression in RAW 264.7 cells treated with/without OxLDL. The transcriptome libraries were constructed using the NEB adapters and were sequenced on at 150 nucleotide read length using the paired-end chemistry. The raw reads were subjected to Adapter and low-quality reads removal by Trimmomatic -0.36v. The raw reads were subjected to contamination [structural RNA / low complexity sequences] removal by mapping with bowtie 2-2.2.1. The decontaminated data set was mapped to the mouse genome. Reads mapping to gene list were counted using feature count module of sub reads package. The read counts were normalized in DESeq2-3.5, and subject to differential expression analysis. Differentially expressed genes were selected based on log2-ratio change with p-value <0.05 (Student’s t-test, unpaired). Hierarchical clustering was performed with the programs Cluster (uncentered correlation; average linkage clustering) and Treeview. Results: To gain a deeper understanding of the role of PHLPP1 in lipid metabolism in macrophages, we performed mRNA Seq analysis to assess the gene expression changes in a mouse macrophage cell line. The experiment has been carried out in triplicates. Alignment of the reads showed 97% alignment to the reference mouse genome. Identification of the differentially expressed genes were then carried out by DESeq2 version 1.2.10 with stringent criteria (FDR <0.05% with 2 fold up and down regulation) which reveals in control treated vs. control (121-down, 396-Up), Test vs. Control - (326-down, 569 Up) and Test treated vs. control treated (1314-down, 1328 up) of DEG to be altered in expression respectively. Inference: RNA-seq analysis revealed that PHLPP1 knockdown parallel with OxLDL treatment resulted in diminished expression profile of cholesterol biosynthesis and lipid metabolism genes.
2022-01-09 | GSE193132 | GEO
Project description:Nuclear receptors, such as liver X receptors (LXRs) and sterol regulatory element-binding proteins (SREBPs), are key regulators of lipogenic genes, including fatty acid synthase (FASN). It has been reported that several oxycholesterols (OCs) act as LXR ligands; however, it is unclear whether all OC molecular species act as ligands. We previously demonstrated that the absorption rate of dietary 6-ketocholestanol (6-keto), an oxycholesterol, is the highest of all the OCs using thoracic lymph duct-cannulated rats. However, limited information is available about the physiological significance of 6-keto. In this study, we investigated whether treatment with 6-keto increases intracellular triacylglycerol (TAG) levels through up-regulation of lipogenic gene expression in HepG2 cells. 6-Keto treatment significantly reduced intracellular TAG levels through down-regulation of lipogenic genes including FASN. Although 6-keto significantly suppressed FASN gene promoter activities, the action was completely diminished when mutations were present in the SREBP promoter site. TO901317 (TO) significantly increased FASN gene promoter activities, whereas simultaneous treatment with TO and 6-keto significantly reduced this activity. We also compared the effects of several OCs that are oxidized at the carbon-6 and -7 in the B-ring of cholesterol on FASN gene promoter activities. Similar to 6-keto, 6α-OH and 6β-OH significantly reduced the activity of the FASN gene promoter, which suggests that oxidation of carbon-6 in the B-ring may play an important role in the reduction of FASN expression. Our results indicate that 6-keto suppresses lipid accumulation by decreasing FASN gene expression through SREBP-dependent regulation in HepG2 cells.
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Project description:Insulin resistance (IR), caused by impaired insulin signal and decreased insulin sensitivity, is generally responsible for the pathophysiology of type 2 diabetes mellitus (T2DM). Sesquiterpene glycosides (SGs), the exclusive natural products from loquat leaf, have been regarded as potential lead compounds owing to their high efficacy in hypoglycemia and hypolipidemia. Here, we evaluated the beneficial effects of four single SGs isolated from loquat leaf, including SG1, SG2, SG3 and one novel compound SG4 against palmitic acid-induced insulin resistance in HepG2 cells. SG1, SG3 and SG4 could significantly enhance glucose uptake of insulin-resistant HepG2 cells at non-cytotoxic concentration. Meanwhile, Oil Red O staining showed the decrease of both total cholesterol and triglyceride content, suggesting the amelioration of lipid accumulation by SGs in insulin-resistant HepG2 cells. Further investigations found that the expression levels of phosphorylated AMPK, ACC, IRS-1, and Akt were significantly up-regulated after SGs treatment, on the contrary, the expression levels of SREBP-1 and FAS were significantly down-regulated. Notably, AMPK inhibitor Compound C (CC) blocked the regulative effects, while AMPK activator AICAR mimicked the effects of SGs in PA-treated insulin-resistant HepG2 cells. In conclusion, SGs (SG4>SG1≈SG3>SG2) improved lipid accumulation in insulin-resistant HepG2 cells through the AMPK signaling pathway.
| S-EPMC7680621 | biostudies-literature