scholarly journals Glehnia littoralis Root Extract Inhibits Fat Accumulation in 3T3-L1 Cells and High-Fat Diet-Induced Obese Mice by Downregulating Adipogenic Gene Expression

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Heeok Hong ◽  
Joseph F. dela Cruz ◽  
Won Seob Kim ◽  
Kiyeol Yoo ◽  
Seong Gu Hwang
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Obese Mice ◽  
Intracellular Lipid ◽  
Glehnia Littoralis ◽  
Intracellular Lipid Accumulation ◽  
Adipogenic Gene

Glehnia littoralis has been reported to have several pharmacological properties but no reports describing the antiadipogenic effect of this plant have been published. This study was conducted to investigate the effects of Glehnia littoralis root hot water extract (GLE) and its underlying mechanism on 3T3-L1 cell adipogenesis and in high-fat diet- (HFD-) induced obese mice. We measured intracellular lipid accumulation using oil red O staining in vitro. For in vivo study, twenty-eight C57BL/6J male mice were randomly divided into four groups, Control, HFD, HFD + 1% GLE, and HFD + 5% GLE, which was performed for eight weeks. We determined the expression levels of the adipogenesis-related proteins by RT-PCR and western blotting in HFD-induced obese mice. The GLE dose-dependently inhibited 3T3-L1 adipocyte differentiation and intracellular lipid accumulation in differentiated adipocytes. Further, body weight gain and fat accumulation were significantly lower in the GLE-treated HFD mice than in the untreated HFD mice. GLE treatment suppressed the expression of adipogenic genes such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, fatty acid synthase (aP2), and fatty acid synthase (FAS). These results suggest that the GLE inhibits adipocyte differentiation and intracellular lipid accumulation by downregulating the adipogenic gene expression both in vitro and in vivo.

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals Papain Ameliorates Lipid Accumulation and Inflammation in High-Fat Diet-Induced Obesity Mice and 3T3-L1 Adipocytes via AMPK Activation

2021 ◽  
Vol 22 (18) ◽  
pp. 9885
Author(s):  
Yun-Mi Kang ◽  
Hyun-Ae Kang ◽  
Divina C. Cominguez ◽  
Su-Hyun Kim ◽  
Hyo-Jin An
Keyword(s):  
Lipid Accumulation ◽  
High Fat Diet ◽  
In Vitro Models ◽  
The Body ◽  
Obese Mice ◽  
High Fat ◽  
Oil Accumulation ◽  
Wide Range

Papain is a proteolytic enzyme present in the leaves, fruits, roots, and latex of the Carica papaya (papaya) plant. Although it exhibits a wide range of activities, there are no reports on the anti-obesity effects of papain. This study examined the anti-obesity effect and obesity-involved anti-inflammatory mechanism of papain in in vivo and in vitro models using high-fat diet (HFD)-induced obese mice and 3T3-L1 preadipocytes. Oral administration of papain reduced HFD-induced weight of the body, liver, and adipose tissues of mice. Papain also reduced hepatic lipid accumulation and adipocyte size. Moreover, serum total cholesterol and triglyceride levels were markedly reduced in papain-treated mice. In addition, papain inhibited the differentiation of preadipocytes and oil accumulation in 3T3-L1 preadipocytes and rat primary preadipocytes. Mechanistically, papain significantly downregulated the protein levels of key adipogenesis regulators and reversed the expression of pro-inflammatory cytokines and adipokines in HFD-induced obese mice and 3T3-L1 preadipocytes. Papain also markedly enhanced activation of the AMP-activated protein kinase pathway in both models. Collectively, these results suggest that papain exerts anti-obesity effects in HFD-induced mice and 3T3-L1 preadipocytes by regulating levels of adipogenic factors involved in lipid metabolism and inflammation; thus, it could be useful in the prevention and treatment of obesity.

scholarly journals Effects of fisetin on mouse lipid metabolism in vitro and in vivo

2014 ◽  
Vol 4 (10) ◽  
pp. 429 ◽  
Author(s):  
Tomoaki Yonesaka ◽  
Kaoru Yoshida ◽  
Shunsuke Iizuka ◽  
Hiromi Hagiwara
Keyword(s):  
Polymerase Chain Reaction ◽  
Body Weight ◽  
Real Time ◽  
Lipid Accumulation ◽  
Chain Reaction ◽  
Intracellular Lipid ◽  
Intracellular Lipid Accumulation ◽  
Polymerase Chain

Objective: The aim of this study was to investigate the anti-obesity effects of the polyphenol fisetin in 3T3-L1 preadipocytes and C57BL/6 female mice that were fed a high-fat diet (HFD).Background: Polyphenols, such as sakuranetin, hesperetin, tea catechin, and quercetin, reportedly regulate adipocyte differentiation in 3T3-L1 cells. Furthermore, green tea, apple, and molokheiya polyphenols exhibit anti-obesity activities in HFD-treated obese rats or mice. Fisetin is abundant in plants, fruits, and vegetables and exhibits multiple biological activities, such as the inhibition of prostate cancer growth, neuroprotection, and protection against osteoporosis. In addition, fisetin regulates obesity by targeting mammalian target of rapamycin complex 1 signaling, which is a central mediator of lipid biosynthesis.Materials and methods: (1) in vitro experiments; we investigated the effects of fisetin on intracellular lipid accumulation and glycerol-3-phosphate activity during the differentiation of 3T3-L1 cells. We monitored expression of adipogenetic related-genes in 3T3-L1 cells by real-time polymerase-chain-reaction. (2) in vivo experiments; we examined the effects of fisetin on anti-obesity activities in C57BL/6 female mice that were fed a HFD.Results: Fisetin inhibited intracellular lipid accumulation and glycerol-3-phosphate activity during the differentiation of 3T3-L1 cells in a dose-dependent manner (50-75 M). In addition, real-time polymerase-chain-reaction revealed that this compound suppressed the expression of peroxisome proliferator-activated receptor γ (PPARγ), adipocyte protein 2, and perilipin mRNAs in 3T3-L1 cells. In contrast, anti-obesity activities, such as reduction of body weight and fat tissue, and improvements in obesity-related blood biochemical parameters and fatty liver, were not observed in HFD-induced mice treated with fisetin (20 mg/kg body weight) by intraperitoneal injections twice per week for 8 weeks.Conclusions: Fisetin exerted anti-adipogenic activities by inhibiting the expression of PPARγ mRNA in 3T3-L1 preadipocytes. However, fisetin (20 mg/kg body weight) did not affect HFD-induced obesity. Our findings indicated that fisetin could be used as an effective remedy in the treatment of the symptoms of obesity.Keywords: Fisetin, MC3T3-L1 cells, Fatty accumulation, PPARγ, Obesity, Anti-obesity activity

scholarly journals Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

2021 ◽  
Author(s):  
sheng Qiu ◽  
Zerong Liang ◽  
Qinan Wu ◽  
Miao Wang ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

scholarly journals 905 FASN prevents immunogenicity of irradiated glioblastoma by inhibiting ER stress

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A950-A950
Author(s):  
Mara De Martino ◽  
Camille Daviaud ◽  
Claire Vanpouille-Box
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Immune Escape ◽  
De Novo ◽  
Lipid Synthesis ◽  
Adult Brain ◽  
Immune Recognition

BackgroundGlioblastoma (GBM) is the most aggressive and incurable adult brain tumor. Radiation therapy (RT) is an essential modality for GBM treatment and is recognized to stimulate anti-tumor immunity by inducing immunogenic cell death (ICD) subsequent to endoplasmic reticulum (ER) stress. However, RT also exacerbates potent immunosuppressive mechanisms that facilitate immune evasion. Notably, increased de novo lipid synthesis by the fatty acid synthase (FASN) is emerging as a mechanism of therapy resistance and immune escape. Here, we hypothesize that RT induces FASN to promote GBM survival and evade immune recognition by inhibiting ER stress and ICD.MethodsTo determine if lipid synthesis is altered in response to RT, we first assessed FASN expression by western blot (WB) and lipid accumulation by BODIPY staining in murine (CT2A and GL261) and human (U118) GBM cell lines. Next, FASN expression was blocked in CT2A cells using CRISPR-Cas9 or an inducible shRNA directed against Fasn to evaluate ICD and ER stress markers by ELISA, WB, and electron microscopy. Finally, CT2AshFASN cells or its non-silencing control (CT2AshNS) were orthotopically implanted and FASN knockdown was induced by feeding the mice with doxycycline. The immune contexture was determined by in situ immunofluorescence (n=3/group). Remaining mice were followed for survival (n=7/group).ResultsWe found that in vitro irradiation of GBM cells induces lipid accumulation in a dose-dependent fashion; an effect that is magnified over time lasting at least 6/7 days. Consistent with these findings, FASN expression was upregulated in irradiated GBM cells. Confirming the role of FASN, RT-induced accumulation of lipids was reverted when GBM cells were incubated with a FASN inhibitor. Next, we found that FASN ablation in CT2A cells induces mitochondria disruption and was sufficient to increase the expression of the ER stress makers BIP and CHOP. Along similar lines, shFASN enhances the secretion of the ICD markers HMGB1, IFN-beta and CXCL10 in irradiated CT2A cells. In vivo, CT2AshFASN tumors presented increased infiltration of CD11c+ cells and CD8+ T cells, consistent with prolonged mice survival (56 days vs. 28 days for CT2AshNS). Importantly, 43% of CT2AshFASN-bearing mice remained tumor-free for more than 70 days, while none of the CT2AshNS-bearing mice survived.ConclusionsAltogether, our data suggest that FASN-mediated lipid synthesis is an important mechanism to prevent ER stress, ICD, and anti-tumor immune responses in GBM. While much work remains to be done, our data propose FASN as a novel therapeutic target to overcome immunosuppression and sensitize GBM to immunotherapies.

scholarly journals Curcumin improves glycolipid metabolism through regulating peroxisome proliferator activated receptor γ signalling pathway in high-fat diet-induced obese mice and 3T3-L1 adipocytes

2017 ◽  
Vol 4 (11) ◽  
pp. 170917 ◽  
Author(s):  
Yanyun Pan ◽  
Dandan Zhao ◽  
Na Yu ◽  
Tian An ◽  
Jianan Miao ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Signalling Pathway ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glycolipid Metabolism

Curcumin is an active component derived from Curcuma longa L. which is a traditional Chinese medicine that is widely used for treating metabolic diseases through regulating different molecular pathways. Here, in this study, we aimed to comprehensively investigate the effects of curcumin on glycolipid metabolism in vivo and in vitro and then determine the underlying mechanism. Male C57BL/6 J obese mice and 3T3-L1 adipocytes were used for in vivo and in vitro study, respectively. Our results demonstrated that treatment with curcumin for eight weeks decreased body weight, fat mass and serum lipid profiles. Meanwhile, it lowered fasting blood glucose and increased the insulin sensitivity in high-fat diet-induced obese mice. In addition, curcumin stimulated lipolysis and improved glycolipid metabolism through upregulating the expressions of adipose triglyceride lipase and hormone-sensitive lipase, peroxisome proliferator activated receptor γ/α (PPARγ/α) and CCAAT/enhancer binding proteinα (C/EBPα) in adipose tissue of the mice. In differentiated 3T3-L1 cells, curcumin reduced glycerol release and increased glucose uptake via upregulating PPARγ and C/EBPα. We concluded that curcumin has the potential to improve glycolipid metabolism disorders caused by obesity through regulating PPARγ signalling pathway.

scholarly journals Maternal Diabetes Leads to Unphysiological High Lipid Accumulation in Rabbit Preimplantation Embryos

Endocrinology ◽  
2014 ◽  
Vol 155 (4) ◽  
pp. 1498-1509 ◽  
Author(s):  
Maria Schindler ◽  
Mareike Pendzialek ◽  
Alexander Navarrete Santos ◽  
Torsten Plösch ◽  
Stefanie Seyring ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Binding Protein ◽  
Maternal Diabetes ◽  
Preimplantation Embryos ◽  
Intracellular Lipid ◽  
Fatty Acid Binding ◽  
Intracellular Lipid Accumulation

According to the “developmental origin of health and disease” hypothesis, the metabolic set points of glucose and lipid metabolism are determined prenatally. In the case of a diabetic pregnancy, the embryo is exposed to higher glucose and lipid concentrations as early as during preimplantation development. We used the rabbit to study the effect of maternal diabetes type 1 on lipid accumulation and expression of lipogenic markers in preimplantation blastocysts. Accompanied by elevated triglyceride and glucose levels in the maternal blood, embryos from diabetic rabbits showed a massive intracellular lipid accumulation and increased expression of fatty acid transporter 4, fatty acid–binding protein 4, perilipin/adipophilin, and maturation of sterol-regulated element binding protein. However, expression of fatty acid synthase, a key enzyme for de novo synthesis of fatty acids, was not altered in vivo. During a short time in vitro culture of rabbit blastocysts, the accumulation of lipid droplets and expression of lipogenic markers were directly correlated with increasing glucose concentration, indicating that hyperglycemia leads to increased lipogenesis in the preimplantation embryo. Our study shows the decisive effect of glucose as the determining factor for fatty acid metabolism and intracellular lipid accumulation in preimplantation embryos.

scholarly journals Semen Cuscutae Administration Improves Hepatic Lipid Metabolism and Adiposity in High Fat Diet-Induced Obese Mice

Nutrients ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 3035
Author(s):  
Jiyoung Moon ◽  
Min Jin Ha ◽  
Min-Jeong Shin ◽  
Oh Yoen Kim ◽  
Eun Hye Yoo ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Whole Body ◽  
No Production ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
High Fat ◽  
Hepatic Lipid

Since arginase has been shown to compete with nitric oxide (NO) synthase, emerging evidence has reported that arginase inhibition improves obesity by increasing NO production. Semen cuscutae (SC), which is a well-known Chinese medicine, has multiple biological functions such as anti-oxidant function and immune regulation. In this study, we investigated whether the SC as a natural arginase inhibitor influences hepatic lipid abnormalities and whole-body adiposity in high-fat diet (HFD)-induced obese mice. The lipid accumulation was significantly reduced by SC treatment in oleic acid-induced hepatic steatosis in vitro. Additionally, SC supplementation substantially lowered HFD-induced increases in arginase activity and weights of liver and visceral fat tissue, while increasing hepatic NO. Furthermore, elevated mRNA expressions of sterol regulatory element-binding transcription factor 1 (SREBP-1c), fatty-acid synthase (FAS), peroxisome proliferator-activated receptor-gamma (PPAR-γ)1, and PPAR-γ2 in HFD-fed mice were significantly attenuated by SC supplementation. Taken together, SC, as a novel natural arginase inhibitor, showed anti-obesity properties by modulating hepatic arginase and NO production and metabolic pathways related to hepatic triglyceride (TG) metabolism.

scholarly journals Sulfation of 25-hydroxycholesterol regulates lipid metabolism, inflammatory responses, and cell proliferation

2014 ◽  
Vol 306 (2) ◽  
pp. E123-E130 ◽  
Author(s):  
Shunlin Ren ◽  
Yanxia Ning
Keyword(s):  
Cell Proliferation ◽  
Lipid Metabolism ◽  
Inflammatory Responses ◽  
Regulatory Element ◽  
Intracellular Lipid ◽  
Nonalcoholic Fatty Liver ◽  
Key Enzyme ◽  
Intracellular Lipid Accumulation

Intracellular lipid accumulation, inflammatory responses, and subsequent apoptosis are the major pathogenic events of metabolic disorders, including atherosclerosis and nonalcoholic fatty liver diseases. Recently, a novel regulatory oxysterol, 5-cholesten-3b, 25-diol 3-sulfate (25HC3S), has been identified, and hydroxysterol sulfotransferase 2B1b (SULT2B1b) has been elucidated as the key enzyme for its biosynthesis from 25-hydroxycholesterol (25HC) via oxysterol sulfation. The product 25HC3S and the substrate 25HC have been shown to coordinately regulate lipid metabolism, inflammatory responses, and cell proliferation in vitro and in vivo. 25HC3S decreases levels of the nuclear liver oxysterol receptor (LXR) and sterol regulatory element-binding proteins (SREBPs), inhibits SREBP processing, subsequently downregulates key enzymes in lipid biosynthesis, decreases intracellular lipid levels in hepatocytes and THP-1-derived macrophages, prevents apoptosis, and promotes cell proliferation in liver tissues. Furthermore, 25HC3S increases nuclear PPARγ and cytosolic IκBα and decreases nuclear NF-κB levels and proinflammatory cytokine expression and secretion when cells are challenged with LPS and TNFα. In contrast to 25HC3S, 25HC, a known LXR ligand, increases nuclear LXR and decreases nuclear PPARs and cytosol IκBα levels. In this review, we summarize our recent findings, including the discovery of the regulatory oxysterol sulfate, its biosynthetic pathway, and its functional mechanism. We also propose that oxysterol sulfation functions as a regulatory signaling pathway.

Chrysanthemum indicum Inhibits Adipogenesis and Activates the AMPK Pathway in High-Fat-Diet-Induced Obese Mice

2018 ◽  
Vol 46 (01) ◽  
pp. 119-136 ◽  
Author(s):  
Sarmila Nepali ◽  
Ji-Yun Cha ◽  
Hyeon-Hui Ki ◽  
Hoon-Yeon Lee ◽  
Young-Ho Kim ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Obese Mice ◽  
High Fat ◽  
In Vivo Models ◽  
Garcinia Cambogia ◽  
Chrysanthemum Indicum

Chrysanthemum indicum (CI) is widely distributed in China and many parts of the tropical world, and has been reported to have antibacterial, antiviral, anti-oxidant and immunomodulatory effects, but no information is available on its effects on high fat diet (HFD)-induced obesity. This was undertaken to investigate the mechanism responsible for the effect of ethyl acetate fraction of CI (CIEA) on adipogenesis, in vitro and in vivo models of obesity. In the in vitro study, differentiating 3T3-L1 cells were treated with media to initiate differentiation (MDI) in the presence or absence of CIEA with different concentrations, and in the in vivo study, C57BL/6 mice were fed with HFD and administered CIEA daily for six weeks. Garcinia cambogia (GC) was used as the positive control, and was administered in the same manner as CIEA. Results showed CIEA reduced HFD-induced body weight gain, epididymal white adipose tissue (eWAT), and liver weight. In addition, CIEA significantly decreased serum lipid profiles, including total cholesterol (TC), triglyceride (TG) and low density lipoprotein cholesterol (LDLc) and increased high density lipoprotein cholesterol (HDLc) levels. Furthermore, CIEA also reduced leptin levels and increased adiponectin levels in serum, and significantly decreased peroxisome proliferator-activated receptor [Formula: see text] (PPAR[Formula: see text]) and CCAAT/enhancer-binding protein (C/EPBs) levels, but increased PPAR[Formula: see text] level and the phosphorylation of AMP-activated protein kinase (AMPK) in eWATs and in the liver tissues of HFD fed obese mice. Taken together, these results indicate CIEA might be beneficial for preventing obesity.

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