scholarly journals Effect of Astaxanthin on the Inhibition of Lipid Accumulation in 3T3-L1 Adipocytes via Modulation of Lipogenesis and Fatty Acid Transport Pathways

Molecules ◽  
2020 ◽  
Vol 25 (16) ◽  
pp. 3598
Author(s):  
Mei-Chih Tsai ◽  
Shih-Chien Huang ◽  
Wei-Tang Chang ◽  
Shiuan-Chih Chen ◽  
Chin-Lin Hsu
Keyword(s):  
Fatty Acid ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Transport Pathways ◽  
Fatty Acid Binding ◽  
Triglyceride Accumulation

Obesity is defined as a condition of excessive fat tissue accumulation. It was the major factor most closely associated with lifestyle-related diseases. In the present study, we investigated the effect of astaxanthin on the inhibition of lipid accumulation in 3T3-L1 adipocytes. 3T3-L1 adipocytes were treated with 0–25 µg/mL of astaxanthin for 0–48 h. The result indicated that astaxanthin significantly decreased the oil Red O stained material (OROSM), intracellular triglyceride accumulation, and glycerol 3-phosphate dehydrogenase (GPDH) activity in 3T3-L1 adipocytes (p < 0.05). At the molecular level, astaxanthin significantly down-regulated the mRNA expression of peroxisome proliferator-activated receptor-γ (PPARγ) in 3T3-L1 adipocytes (p < 0.05). Moreover, target genes of PPARγ on the inhibition of lipogenesis, such as Acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), fatty acid binding protein (aP2), cluster of differentiation 36 (CD36), and lipoprotein lipase (LPL) in 3T3-L1 adipocytes were significantly down-regulated at a time-dependent manner (p < 0.05). These results suggested that astaxanthin efficiently suppressed lipid accumulation in 3T3-L1 adipocytes and its action is associated with the down-regulation of lipogenesis-related genes and the triglyceride accumulation in 3T3-L1 adipocytes. Therefore, astaxanthin can be developed as a potential nutraceutical ingredient for the prevention of obesity in a niche market.

Evaluation of anti-adipogenic active homoisoflavonoids from Portulaca oleracea

2019 ◽  
Vol 74 (9-10) ◽  
pp. 265-273 ◽  
Author(s):  
Jung Im Lee ◽  
Jung Hwan Oh ◽  
Chang-Suk Kong ◽  
Youngwan Seo
Keyword(s):  
Fatty Acid ◽  
Crude Extract ◽  
Lipid Accumulation ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Portulaca Oleracea ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding

Abstract This study was performed to isolate antiobesity components from the crude extract of Portulaca oleracea. The crude extract was partitioned into n-hexane, 85% aqueous methanol, n-butanol, and water fractions. Their effects on adipogenic differentiation were evaluated in 3T3-L1 cells. Among the solvent fractions from P. olearacea, the 85% aq. MeOH effectively reduced the levels of lipid accumulation. Further purification of 85% aq. MeOH led to the isolation of the known homoisoflavonoids 1–4, as the active substances. The administration of homoisoflavonoids to adipocyte cells decreased the lipid accumulation and glucose consumption and increased the release of glycerol into culture medium. In particular, homoisoflavonoid 3 effectively down-regulated the adipogenic transcription genes such as peroxisome proliferator activated receptor-γ (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPα), and adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid transport protein 1 (FATP1), and acyl-CoA synthase 1 (ACS1).

scholarly journals Genistin: A Novel Potent Anti-Adipogenic and Anti-Lipogenic Agent

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2042 ◽  
Author(s):  
Yae Rim Choi ◽  
Jaewon Shim ◽  
Min Jung Kim
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Atp Citrate Lyase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Specific Proteins

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.

scholarly journals Lactobacillus plantarumLG42 Isolated from Gajami Sik-Hae Inhibits Adipogenesis in 3T3-L1 Adipocyte

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jeong-Eun Park ◽  
Suk-Heung Oh ◽  
Youn-Soo Cha
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
Binding Protein ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Intracellular Lipid Accumulation ◽  
Glycerol 3 Phosphate Dehydrogenase

We investigated whether lactic acid bacteria isolated from gajami sik-hae (GLAB) are capable of reducing the intracellular lipid accumulation by downregulating the expression of adipogenesis-related genes in differentiated 3T3-L1 cells. The GLAB,Lactobacillus plantarumLG42, significantly decreased the intracellular triglyceride storage and the glycerol-3-phosphate dehydrogenase (GPDH) activity in a dose-dependent manner. mRNA expression of transcription factors like peroxisome proliferator-activated receptor (PPAR)γand CCAAT/enhancer-binding protein (C/EBP)αinvolved in adipogenesis was markedly decreased by the GLAB treatment. Moreover, the GLAB also decreased the expression level of adipogenic markers like adipocyte fatty acid binding protein (aP2), leptin, GPDH, and fatty acid translocase (CD36) significantly. These results suggest that the GLAB inhibits lipid accumulation in the differentiated adipocyte through downregulating the expression of adipogenic transcription factors and other specific genes involved in lipid metabolism.

scholarly journals Catalpol Attenuates Hepatic Steatosis by Regulating Lipid Metabolism via AMP-Activated Protein Kinase Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiang Tian ◽  
Qin Ru ◽  
Qi Xiong ◽  
Ruojian Wen ◽  
Yong Chen
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
Dependent Manner ◽  
Compound C ◽  
Amp Activated Protein Kinase

The increased prevalence of nonalcoholic fatty liver disease (NAFLD), which develops from hepatic steatosis, represents a public health challenge. Catalpol, a natural component extracted from the roots of Radix Rehmanniae, has several pharmacological activities. The present study is aimed at examining whether catalpol prevents hepatic steatosis in cell and animal experiments and elucidating the possible mechanisms. HepG2 cells were treated with 300 μM palmitate (PA) and/or catalpol for 24 h in vitro, and male C57BL/6J mice fed a high-fat diet (HFD) were administered catalpol for 18 weeks in vivo. The results revealed that catalpol significantly decreased lipid accumulation in PA-treated HepG2 cells. Moreover, catalpol drastically reduced body weight and lipid accumulation in the liver, whereas it ameliorated hepatocyte steatosis in HFD-fed mice. Notably, catalpol remarkably promoted the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, catalpol repressed the expressions of lipogenesis-associated genes such as sterol regulatory element-binding protein 1c and fatty acid synthase but promoted the expressions of genes associated with fatty acid β-oxidation such as peroxisome proliferator-activated receptor α together with its target genes carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 (ACOX1). However, the preincubation of the HepG2 cells with compound C (10 μM), an AMPK inhibitor, prevented catalpol-mediated beneficial effects. These findings suggest that catalpol ameliorates hepatic steatosis by suppressing lipogenesis and enhancing fatty acid β-oxidation in an AMPK-dependent manner. Therefore, catalpol has potential as a novel agent in the treatment of NAFLD.

scholarly journals Anti-adipogenic Effect of Homoisoflavonoids from Portulaca Oleracea (P06-015-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
JungIm Lee ◽  
JungHwan Oh ◽  
Fatih Karadeniz ◽  
Chang-Suk Kong ◽  
Youngwan Seo
Keyword(s):  
Fatty Acid ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Glucose Consumption ◽  
Portulaca Oleracea ◽  
Women In Science ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Inhibitory Effects ◽  
Fatty Acid Binding

Abstract Objectives To search for anti-adipogenic components from natural plants, this study evaluated inhibitory effects of active components from Portulaca oleracea on adipogenic differentiation. Methods The crude extract was partitioned into n-hexane, 85% aqueous methanol, n-butanol, and water fractions. By anti-adipogenic assay-guided isolation method, 4 kinds of homoisoflavonoids (1–4) were isolated from 85%aq. MeOH fraction. Their inhibitory effects on adipogenic differentiation were evaluated by Oil red O intracellular lipid staining, and measuring glycerol release, glucose consumption and adiopogenesis-related gene expression in 3T3-L1 cells. Results The administration of homoisoflavonoids 1–4 to adipocyte cells decreased the lipid accumulation and glucose consumption, and increased the release of glycerol into culture medium. In particular, homoisoflavonoid 3 effectively down-regulated the adipogenic transcription genes such as peroxisome proliferator activated receptor-γ (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPα), and adipogenic target genes such as fatty acid binding protein 4 (FABP4), fatty acid transport protein 1 (FATP1), and acyl-CoA synthase 1 (ACS1). Conclusions This study suggested that homoisoflavonoids 3 held notable potential to be used for the treatment and prevention of obesity and related disorders. Funding Sources This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education and the Center for Women In Science, Engineering and Technology (WISET) Grant funded by the Ministry of Science and ICT (MSIT) under the Program for Returners into R&D.

scholarly journals Chrysanthemum morifolium Flower Extract Inhibits Adipogenesis of 3T3-L1 Cells via AMPK/SIRT1 Pathway Activation

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2726
Author(s):  
Mak-Soon Lee ◽  
Yangha Kim
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Chrysanthemum Morifolium ◽  
Hot Water ◽  
Sirtuin 1 ◽  
Dependent Manner ◽  
Fatty Acid Binding

Chrysanthemum (Chrysanthemum morifolium Ramat) flowers (CF) are widely consumed as herbal tea in many countries, including China. The aim of the present study was to examine the anti-adipogenic effect of hot water extraction of CF (HCF) on 3T3-L1 cells and their underlying cellular mechanisms. HCF treatment inhibited lipid accumulation under conditions that did not show the toxicity of 3T3-L1 adipocytes. The activity of glycerol-3-phosphate dehydrogenase (GPDH), which plays an important role in glycerol lipid metabolism, was also reduced by HCF. Adipogenesis/lipogenesis-related mRNA expression levels of peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (CEBP-α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid-binding protein 4 (FABP4), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS) were suppressed by HCF in a dose-dependent manner. Moreover, HCF increased activities of AMP-activated protein kinase (AMPK) and sirtuin 1 (SIRT1), involved in lipid metabolism. These findings suggest that HCF inhibits adipocyte lipid accumulation through suppression of adipogenesis/lipogenesis-related gene expression and activation of the AMPK/SIRT1 pathway. Therefore, it suggests that HCF may be used as a potentially beneficial plant material for preventing obesity.

scholarly journals Regulation of cardiac fatty acids metabolism in transgenic mice overexpressing bovine GH

2009 ◽  
Vol 201 (3) ◽  
pp. 419-427 ◽  
Author(s):  
Fausto Bogazzi ◽  
Francesco Raggi ◽  
Federica Ultimieri ◽  
Dania Russo ◽  
Aldo D'Alessio ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transgenic Mice ◽  
Fatty Acid Transport ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Fatty Acid Binding ◽  
Chain Acyl ◽  
Fatty Acids Metabolism ◽  
Key Enzyme ◽  
Key Steps

Cardiac energy metabolism depends mainly on fatty acid (FA) oxidation; however, regulation of FA metabolism in acromegalic (Acro) heart is unknown. The aim of the study was to evaluate cardiac expression of key proteins of FA metabolism in young and elder transgenic mice overexpressing bovine GH Acro. Expression of proteins regulating FA entry into the cells, their uptake by mitochondria and β-oxidation were evaluated by western blot, while FA content by Fourier transform infrared microspectrometry. Regulatory mechanisms of key steps of FA metabolism were also studied. The expression of plasma-membrane FA carriers (fatty acid-binding protein and fatty acid transport protein-1) and acylCoA synthetase was higher in young and lower in elder Acro than in corresponding controls; likewise, expression of cytoplasm to mitochondria-1 (CPT-1), the key enzyme of mitochondrial FA uptake, and that of medium-chain acyl-CoA dehydrogenase and long-chain acyl-CoA dehydrogenase, two regulatory β-oxidation dehydrogenases, followed a similar pattern. FA content was lower in young and higher in elder Acro than in wild-type, suggesting an increased utilisation in young animals. GH regulated expression of key proteins of FA metabolism through changes in peroxisome proliferator-activated receptor α (PPARα) expression, which varied accordingly. GH effect was confirmed by treatment of Acro mice with a receptor antagonist, which abolished changes in key proteins of FA metabolism in young Acro. GH increased phosphorylation of AMP-activated protein kinase and anti-acetyl-CoA-carboxylase, two regulatory kinases, leading to lower CPT-1 inhibition by malonyl-CoA, and intervened in regulating PPARα expression through the ERK 1/2 pathway. In conclusion, chronic GH excess increased FA metabolism in the young age, whereas its action was overwhelmed in elder ages likely by GH-independent mechanisms, leading to reduced expression of key enzyme of FA metabolism.

SUMO modification selectively regulates transcriptional activity of peroxisome-proliferator-activated receptor γ in C2C12 myotubes

2010 ◽  
Vol 433 (1) ◽  
pp. 155-161 ◽  
Author(s):  
Sung Soo Chung ◽  
Byung Yong Ahn ◽  
Min Kim ◽  
Jun Ho Kho ◽  
Hye Seung Jung ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Transcriptional Activity ◽  
Target Genes ◽  
C2c12 Cells ◽  
C2c12 Myotubes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mouse Muscle ◽  
Fatty Acid Binding ◽  
Specific Protease

PPAR (peroxisome-proliferator-activated receptor) γ, a nuclear receptor, can be conjugated with SUMO (small ubiquitin-like modifier), which results in the negative regulation of its transcriptional activity. In the present study, we tested whether de-SUMOylation of PPARγ affects the expression of PPARγ target genes in mouse muscle cells and investigated the mechanism by which de-SUMOylation increases PPARγ transcriptional activity. We found that the SUMO-specific protease SENP2 [SUMO1/sentrin/SMT3 (suppressor of mif two 3 homologue 1)-specific peptidase 2] effectively de-SUMOylates PPARγ–SUMO conjugates. Overexpression of SENP2 in C2C12 cells increased the expression of some PPARγ target genes, such as FABP3 (fatty-acid-binding protein 3) and CD36 (fatty acid translocase), both in the absence and presence of rosiglitazone. In contrast, overexpression of SENP2 did not affect the expression of another PPARγ target gene ADRP (adipose differentiation-related protein). De-SUMOylation of PPARγ increased ChIP (chromatin immunoprecipitation) of both a recombinant PPRE (PPAR-response element) and endogenous PPREs of the target genes CD36 and FABP3, but ChIP of the PPRE in the ADRP promoter was not affected by SENP2 overexpression. In conclusion, these results indicate that SENP2 de-SUMOylates PPARγ in myotubes, and de-SUMOylation of PPARγ selectively increases the expression of some PPARγ target genes.

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.

PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes

2005 ◽  
Vol 288 (6) ◽  
pp. E1195-E1205 ◽  
Author(s):  
Susan E. Schadinger ◽  
Nancy L. R. Bucher ◽  
Barbara M. Schreiber ◽  
Stephen R. Farmer
Keyword(s):  
Fatty Acid ◽  
Cell Line ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Binding Protein ◽  
Regulatory Element ◽  
Fatty Acid Binding ◽  
Triacylglycerol Synthesis

Peroxisome proliferator-activated receptor-γ (PPARγ) is considered to be one of the master regulators of adipocyte differentiation. PPARγ2 is abundantly expressed in mature adipocytes and is elevated in the livers of animals that develop fatty livers. The aim of this study was to determine the ability of PPARγ2 to induce lipid accumulation in hepatocytes and to delineate molecular mechanisms driving this process. The hepatic cell line AML-12 was used to generate a cell line stably expressing PPARγ2. Oil Red O staining revealed that PPARγ2 induces lipid accumulation in hepatocytes. This phenotype is accompanied by a selective upregulation of several adipogenic and lipogenic genes including adipose differentiation-related protein (ADRP), adipocyte fatty acid-binding protein 4, sterol regulatory element-binding protein-1 (SREBP-1), fatty acid synthase (FAS), and acetyl-CoA carboxylase, genes whose expression levels are known to increase in steatotic livers of ob/ob mice. Furthermore, the PPARγ2-regulated induction of both SREBP-1 and FAS parallels an increase in de novo triacylglycerol synthesis in hepatocytes. Triacylglycerol synthesis and lipid accumulation are further enhanced by culturing hepatocytes with troglitazone in the absence of exogenous lipids. These results correspond with an increase in the lipid droplet protein, ADRP, and the data demonstrate that ADRP functions to coat lipid droplets in hepatocytes as observed by confocal microscopy. Taken together, these observations propose a role for PPARγ2 as an inducer of steatosis in hepatocytes and suggest that this phenomenon occurs through an induction of pathways regulating de novo lipid synthesis.

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