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

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.

Download Full-text

Dietary threonine supplementation improves hepatic lipid metabolism of Pekin ducks

Animal Production Science ◽

10.1071/an17633 ◽

2019 ◽

Vol 59 (4) ◽

pp. 673 ◽

Cited By ~ 3

Author(s):

Y. Jiang ◽

X. D. Liao ◽

M. Xie ◽

J. Tang ◽

S. Y. Qiao ◽

...

Keyword(s):

Fatty Acid ◽

Lipid Metabolism ◽

Fatty Acid Synthase ◽

Binding Protein ◽

Initiation Factor ◽

Pekin Duck ◽

Hepatic Lipid Metabolism ◽

Fatty Acid Binding ◽

Hepatic Lipid ◽

Pekin Ducks

The present study was conducted to evaluate the regulatory role of threonine (Thr) on hepatic lipid metabolism by determining the effects of dietary Thr concentration on lipid deposition and on genes related to lipid expression in the liver of Pekin duck. In total, 240 1-day-old ducklings were randomly allocated according to the average bodyweight to one of five dietary treatments with six replicate cages of eight birds per cage for each treatment. Birds were fed diets with 0.52%, 0.59%, 0.66%, 0.73% and 0.80% Thr (as-fed basis) from 1 to 21 days of age respectively. The results showed that dietary Thr supplementation increased average daily gain (P < 0.0001), average daily feed intake (P < 0.0001) and abdominal fat percentage (P < 0.04), while it decreased feed to gain ratio (P < 0.0001), the hepatic contents of total lipid (P < 0.003) and triglycerides (P < 0.003) of Pekin ducks. However, dietary Thr supplementation had no influence (P > 0.05) on the concentration of hepatic cholesterol, and plasma amino acids and biochemical parameters of Pekin ducks. Moreover, Thr-unsupplemented control diet upregulated (P < 0.05) hepatic gene expression related to lipid uptake (fatty acid-binding protein, apolipoprotein A4, lipoprotein lipase), fatty acid synthesis (sterol regulatory element-binding protein 1c, malic enzyme), fatty acid β-oxidation (peroxisome proliferator-activated receptor α, fatty acyl– coenzyme A (CoA) oxidase), ketogenesis (hydroxymethylglutaryl–CoA synthase 1, and acetyl–CoA synthetase1), responsive genes to amino acid deficiency (general control non-derepressible 2 (GCN2), GCN1, eukaryotic initiation factor 2α, impact RWD domain protein (IMPACT)), and triglyceride transport (apolipoprotein B) of Pekin ducks. In addition, dietary Thr deficiency had no effect on the expression of stearoyl CoA desaturase, fatty acid synthase, and ATP–citrate lyase in the liver of Pekin ducks. It is suggested that dietary Thr supplementation improved hepatic lipid metabolism of Pekin ducks by regulating lipid synthesis, transport and oxidation.

Download Full-text

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

Molecules ◽

10.3390/molecules25092042 ◽

2020 ◽

Vol 25 (9) ◽

pp. 2042 ◽

Cited By ~ 1

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.

Download Full-text

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

BioMed Research International ◽

10.1155/2013/460927 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 11

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.

Download Full-text

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

Endocrinology ◽

10.1210/en.2013-1760 ◽

2014 ◽

Vol 155 (4) ◽

pp. 1498-1509 ◽

Cited By ~ 15

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.

Download Full-text

PPARγ2 regulates lipogenesis and lipid accumulation in steatotic hepatocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00513.2004 ◽

2005 ◽

Vol 288 (6) ◽

pp. E1195-E1205 ◽

Cited By ~ 241

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.

Download Full-text

Unconventional Secretion of Adipocyte Fatty Acid Binding Protein 4 Is Mediated By Autophagic Proteins in a Sirtuin-1–Dependent Manner

Diabetes ◽

10.2337/db18-1367 ◽

2019 ◽

Vol 68 (9) ◽

pp. 1767-1777 ◽

Cited By ~ 5

Author(s):

Ajeetha Josephrajan ◽

Ann V. Hertzel ◽

Ellie K. Bohm ◽

Michael W. McBurney ◽

Shin-Ichiro Imai ◽

...

Keyword(s):

Fatty Acid ◽

Fatty Acid Binding Protein ◽

Binding Protein ◽

Sirtuin 1 ◽

Dependent Manner ◽

Fatty Acid Binding ◽

Acid Binding Protein ◽

Unconventional Secretion ◽

Autophagic Proteins

Download Full-text

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

Molecules ◽

10.3390/molecules25163598 ◽

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.

Download Full-text

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

Nutrients ◽

10.3390/nu12123753 ◽

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.

Download Full-text

Anti-Adipogenic Effect of Neferine in 3T3-L1 Cells and Primary White Adipocytes

Nutrients ◽

10.3390/nu12061858 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1858

Author(s):

Miey Park ◽

Jinyoung Han ◽

Hae-Jeung Lee

Keyword(s):

Fatty Acid ◽

Fatty Acid Synthase ◽

Binding Protein ◽

Regulatory Element ◽

Antioxidant Properties ◽

Adenosine Monophosphate ◽

Sirtuin 1 ◽

Acid Oxidation ◽

Peroxisome Proliferator ◽

Dependent Manner

Neferine, an alkaloid component extracted from lotus seed embryos, is known for its anti-inflammatory, anticancer, and antioxidant properties. However, the anti-adipogenic activity of neferine has not been thoroughly investigated. In this study, neferine was found to inhibit lipid accumulation in a dose-dependent manner during the differentiation of 3T3-L1 cells without inducing cytotoxicity. Real-time polymerase chain reaction and immunoblot analysis revealed the downregulation in the expression of peroxisome proliferator activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) and the upregulation in carnitine palmitoyltransferase-1 (CPT-1) and sirtuin 1 (SIRT1) levels following neferine treatment. Furthermore, neferine increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which is an important regulator of fatty acid oxidation. Our result indicates that neferine attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling. Therefore, neferine may serve as a therapeutic candidate for obesity treatment.

Download Full-text

Red Pepper Seed Inhibits Differentiation of 3T3-L1 Cells during the Early Phase of Adipogenesis via the Activation of AMPK

The American Journal of Chinese Medicine ◽

10.1142/s0192415x18500064 ◽

2018 ◽

Vol 46 (01) ◽

pp. 107-118 ◽

Cited By ~ 3

Author(s):

Hwa-Jin Kim ◽

Mi-Kyoung You ◽

Ziyun Wang ◽

Hyeon-A Kim

Keyword(s):

Fatty Acid ◽

Early Phase ◽

Fatty Acid Synthase ◽

Early Stage ◽

Binding Protein ◽

Water Extract ◽

Red Pepper ◽

Fatty Acid Binding ◽

Compound C ◽

Pepper Seed

Obesity is the main risk factor for metabolic syndromes and there has been an upsurge in demand for effective therapeutic strategies. This study investigated the effect of red pepper seed water extract (RPS) on the process of differentiation in 3T3-L1 adipocytes. RPS treatment significantly suppressed cellular lipid accumulation and reduced the expression of adipocytes-associated proteins, peroxisome proliferator-activated receptor-[Formula: see text] (PPAR-[Formula: see text]), CCAAT/enhancer-binding proteins [Formula: see text] (C/EBP [Formula: see text]), sterol regulatory element binding protein-1c (SREBP-1c), as well as fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4). The inhibitory effect of RPS on differentiation was mainly through the modulation of the C/EBP [Formula: see text] and C/EBP [Formula: see text] expression at the early phase of differentiation. Moreover, at the early phase of differentiation, RPS markedly increased the phosphorylation of AMP-activated protein kinase (AMPK). Such enhancing effect of RPS was abolished in the presence of compound C. Our results suggest that activation of AMPK at early stage of adipogenesis is involved in the anti-adipogenesis effect of RPS.

Download Full-text