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.

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 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 The effect of dietary docosahexaenoic acid on the expression of lipogenic genes in broilers

2007 ◽  
Vol 58 (2) ◽  
pp. 153 ◽  
Author(s):  
H. J. Chin ◽  
Y. H. Ko ◽  
T. F. Shen ◽  
S. T. Ding
Keyword(s):  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Daily Weight Gain ◽  
Feed Conversion ◽  
Lipogenic Genes ◽  
Triacylglycerol Synthesis

The objectives of this work were to determine the effects of dietary fungal docosahexaenoic acid (DHA) on tissue DHA concentration and lipogenic gene expression in broilers. A fungal (SR-21) meal product containing 31.5% total fat and 32.7% DHA (% of total fatty acids) was fed to chicken broilers at 0, 1, or 3% for 3 weeks. A diet with 1% DHA oil (containing 40% DHA) was also fed to chicken broilers as a positive control. Dietary fungal meal supplementation (3%) improved daily weight gain, food intake, and feed conversion ratio. The fungal meal supplementation increased dietary DHA content and consequently increased the DHA content in plasma, breast muscle (Pectoralis major), and livers in the broilers. The plasma triacylglycerol concentration was decreased by the supplementation of dietary DHA. The data indicate that the dietary DHA treatment modified certain aspects of the lipid metabolism, especially pathways related to triacylglycerol synthesis. Indeed, both the 1% DHA oil and 3% fungal meal treatments decreased the hepatic lipogenic transcription factor sterol regulatory element binding protein 1 (SREBP1) mRNA relative abundance, suggesting that dietary DHA supplementation decreases SREBP1 gene functions. The relative mRNA abundance of the de novo fatty acid synthesis genes, fatty acid synthase and acetyl coenzyme A carboxylase, was reduced by 1% DHA oil and 3% fungal meal treatments, suggesting that dietary DHA supplementation decreases lipogenesis in the livers of the broilers. Taken together, the fungal meal is a suitable dietary supplement to increase tissue DHA content and reduce the expression of hepatic lipogenic genes in broilers.

scholarly journals Sinensol-C Isolated from Spiranthes sinensis Inhibits Adipogenesis in 3T3-L1 Cells through the Regulation of Adipogenic Transcription Factors and AMPK Activation

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4204
Author(s):  
Pei-Hsin Shie ◽  
Chung-Ping Yang ◽  
Guan-Jhong Huang ◽  
Sheng-Yang Wang ◽  
Yueh-Hsiung Kuo
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Medical Condition ◽  
Binding Protein ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Down Regulation ◽  
Fatty Acid Binding ◽  
Spiranthes Sinensis

Obesity is an abnormal medical condition caused by accumulation of body fat that presents negative health impacts. Adipocyte hyperplasia, also known as adipogenesis, is one of the major manifestations of obesity. In the present study, we isolated six phenanthrene derivatives (compounds 1–6) from the ethyl acetate fraction of Spiranthes sinensis and investigated their anti-adipogenic activity. We found that among the six phenanthrene derivatives, compound 6 (sinensol-C) exhibited strong inhibitory activity against intracellular lipid accumulation in 3T3-L1 adipocytes, with an IC50 value of 12.67 μM. Sinensol-C remarkably suppressed the accumulation of lipid droplets and adipogenesis, via down-regulation of adipogenic transcription factors, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), sterol regulatory element binding protein-1 (SREBP-1c), fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4), during adipocyte differentiation in 3T3-L1 cells. In addition, treatment with sinensol-C significantly increased the adenosine monophosphate-activated protein kinase (AMPK) activity in 3T3-L1 cells. Taken together, these data strongly suggest that sinensol-C regulates adiogenesis via down-regulation of adipogenic transcription factors and up-regulation of AMPK. Furthermore, this is the first study that demonstrates that sinensol-C has the capacity to modulate adipogenesis.

scholarly journals Chokeberry Extract and Its Active Polyphenols Suppress Adipogenesis in 3T3-L1 Adipocytes and Modulates Fat Accumulation and Insulin Resistance in Diet-Induced Obese Mice

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1734 ◽  
Author(s):  
Na-Hyun Kim ◽  
Jonghwan Jegal ◽  
Yun Kim ◽  
Jeong-Doo Heo ◽  
Jung-Rae Rho ◽  
...  
Keyword(s):  
Body Weight ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Serum Triglyceride ◽  
Biologically Active ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Fatty Acid Binding

Berries of Aronia melanocarpa (chokeberry) are known to be a rich source of biologically active polyphenols. In the present study, the effects of seven anti-adipogenic polyphenolic phytochemicals isolated from A. melanocarpa methanol extract on adipogenic transcription factors were investigated. Amygdalin and prunasin were found to inhibit 3T3-L1 adipocyte differentiation by suppressing the expressions of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), SREBP1c (sterol regulatory element binding protein 1c), FAS (fatty acid synthase), and aP2 (adipocyte fatty-acid–binding protein). A. melanocarpa extract-treated (100 or 200 mg/kg/day on body weight) high fat diet (HFD)-induced obese mice showed significant decreases in body weight, serum triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) levels and improved insulin sensitivity as compared with HFD controls. This research shows A. melanocarpa extract is potentially beneficial for the suppression of HFD-induced obesity.

Hepatitis B virus X protein induces lipogenic transcription factor SREBP1 and fatty acid synthase through the activation of nuclear receptor LXRα

2008 ◽  
Vol 416 (2) ◽  
pp. 219-230 ◽  
Author(s):  
KyeongJin Kim ◽  
Kook Hwan Kim ◽  
Hyeong Hoe Kim ◽  
JaeHun Cheong
Keyword(s):  
Fatty Acid ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Liver Lipid ◽  
Hepatic Cells ◽  
B Virus

HBV (hepatitis B virus) is a primary cause of chronic liver disease, which frequently results in hepatitis, cirrhosis and ultimately HCC (hepatocellular carcinoma). Recently, we showed that HBx (HBV protein X) expression induces lipid accumulation in hepatic cells mediated by the induction of SREBP1 (sterol-regulatory-element-binding protein 1), a key regulator of lipogenic genes in the liver. However, the molecular mechanisms by which HBx increases SREBP1 expression and transactivation remain to be clearly elucidated. In the present study, we demonstrated that HBx interacts with LXRα (liver X receptor α) and enhances the binding of LXRα to LXRE (LXR-response element), thereby resulting in the up-regulation of SREBP1 and FAS (fatty acid synthase) in the presence or absence of the LXR agonist T0901317 in the hepatic cells and HBx-transgenic mice. Furthermore, HBx also augments the ability to recruit ASC2 (activating signal co-integrator 2), a transcriptional co-activator that controls liver lipid metabolic pathways, to the LXRE with LXRα. These studies place LXRα in a key position within the HBx-induced lipogenic pathways, and suggest a molecular mechanism through which HBV infection can stimulate the SREBP1-mediated control of hepatic lipid accumulation.

scholarly journals Acer tegmentosum Maxim Inhibits Adipogenesis in 3t3-l1 Adipocytes and Attenuates Lipid Accumulation in Obese Rats Fed a High-Fat Diet

Nutrients ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3753
Author(s):  
Hang-Hee Cho ◽  
Soo-Jung Lee ◽  
Sung-Ho Kim ◽  
Sun-Hee Jang ◽  
Chungkil Won ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
High Fat ◽  
Fatty Acid Binding ◽  
Obese Rats

We investigated the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 cells and anti-obesity properties in obese rats fed a high-fat diet (HFD). Cellular lipid content in DMI (dexamethasone, 3–isobutyl–1–methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM (60 ug/mL) caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ) (48%), C/EBPα (66%), and peroxisome proliferator-activated receptor γ (PPARγ) (64%) expressions in 3T3-L1 cells. Moreover, ATM induced a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Protein kinase B (Akt) and glycogen synthase kinase 3β (GSK3β) phosphorylation was also decreased by ATM treatment of 3T3-L1 adipocytes. We investigated the anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with an HFD demonstrated elevations in body weight gain, while the administration of ATM reversed body weight (BW) gains and adipose tissue weights in rats fed an HFD. ATM supplementation caused a decrease in the circulating triglyceride and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obese rats. Epididymal fat exhibited significantly larger adipocytes in the HFD group than it did in the ATM-treated group. These results demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size.

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.

Regulation of fatty acid synthase expression in breast cancer by sterol regulatory element binding protein-1c

2003 ◽  
Vol 282 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Y.u-A.n Yang ◽  
Patrice J. Morin ◽  
Wan Fang Han ◽  
Tinghua Chen ◽  
Daniel M. Bornman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Regulatory Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Regulation of the SREBP transcription factors by mTORC1

2011 ◽  
Vol 39 (2) ◽  
pp. 495-499 ◽  
Author(s):  
Caroline A. Lewis ◽  
Beatrice Griffiths ◽  
Claudio R. Santos ◽  
Mario Pende ◽  
Almut Schulze
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
De Novo ◽  
Regulatory Element ◽  
Cholesterol Biosynthesis ◽  
Mammalian Target Of Rapamycin ◽  
Lipid Biosynthesis ◽  
De Novo Lipogenesis ◽  
Genes Encoding

In recent years several reports have linked mTORC1 (mammalian target of rapamycin complex 1) to lipogenesis via the SREBPs (sterol-regulatory-element-binding proteins). SREBPs regulate the expression of genes encoding enzymes required for fatty acid and cholesterol biosynthesis. Lipid metabolism is perturbed in some diseases and SREBP target genes, such as FASN (fatty acid synthase), have been shown to be up-regulated in some cancers. We have previously shown that mTORC1 plays a role in SREBP activation and Akt/PKB (protein kinase B)-dependent de novo lipogenesis. Our findings suggest that mTORC1 plays a crucial role in the activation of SREBP and that the activation of lipid biosynthesis through the induction of SREBP could be part of a regulatory pathway that co-ordinates protein and lipid biosynthesis during cell growth. In the present paper, we discuss the increasing amount of data supporting the potential mechanisms of mTORC1-dependent activation of SREBP as well as the implications of this signalling pathway in cancer.

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