scholarly journals Flavonoids from Acer okamotoanum Inhibit Adipocyte Differentiation and Promote Lipolysis in the 3T3-L1 Cells

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1920 ◽  
Author(s):  
Ji Hyun Kim ◽  
Sanghyun Lee ◽  
Eun Ju Cho
Keyword(s):  
Fatty Acid Synthase ◽  
Glucose Transporter ◽  
Adipocyte Differentiation ◽  
Adenosine Monophosphate ◽  
Hormone Sensitive Lipase ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Acer Okamotoanum ◽  
Related Proteins

Flavonoids, quercitrin, isoquercitrin (IQ), and afzelin, were isolated from ethyl acetate fraction of Acer okamotoanum. We investigated anti-obesity effects and mechanisms of three flavonoids from A. okamotoanum in the differentiated 3T3-L1 cells. The differentiated 3T3-L1 cells increased triglyceride (TG) contents, compared with non-differentiated normal group. However, treatments of three flavonoids from A. okamotoanum decreased TG contents without cytotoxicity. In addition, they showed significant down-regulation of several adipogenic transcription factors, such as γ-cytidine-cytidine-adenosine-adenosine-thymidine/enhancer binding protein -α, -β, and peroxisome proliferator-activated receptor-γ, compared with non-treated control group. Furthermore, treatment of the flavonoids inhibited expressions of lipogenesis-related proteins including fatty acid synthase, adipocyte protein 2, and glucose transporter 4. Moreover, IQ-treated group showed significant up-regulation of lipolysis-related proteins such as adipose triglyceride lipase and hormone-sensitive lipase. In addition, flavonoids significantly activated 5′-adenosine monophosphate-activated protein kinase (AMPK) compared to control group. In particular, IQ showed higher inhibition of TG accumulation by regulation of pathways related with both adipogenesis and lipolysis, than other flavonoids. The present results indicated that three flavonoids of A. okamotoanum showed anti-obesity activity by regulation of adipocyte differentiation, lipolysis, and AMPK signaling, suggesting as an anti-obesity functional agents.

Methanol Extract of Mongolian Iris bungei Maxim. Stimulates 3T3-L1 Adipocyte Differentiation

2021 ◽  
Vol 21 (7) ◽  
pp. 3943-3949
Author(s):  
Jaegoo Yeon ◽  
Sung-Suk Suh ◽  
Ui-Joung Youn ◽  
Badamtsetseg Bazarragchaa ◽  
Ganbold Enebish ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Adipocyte Differentiation ◽  
Methanol Extract ◽  
Regulatory Element ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor

Iris bungei Maxim. (IB), which is native to China and Mongolia, is used as a traditional medicine for conditions such as inflammation, cancer, and bacterial infections. However, the effects of Iris bungei Maxim. on adipocyte differentiation have not been studied. In the present study, we first demonstrated the molecular mechanisms underlying the adipogenic activity of the methanol extract of Mongolian I. bungei Maxim. (IB). IB significantly enhanced intracellular lipid accumulation and adipocyte differentiation in 3T3-L1 preadipocytes in a concentration-dependent manner. Moreover, IB markedly stimulated the expression of genes related to adipogenesis such as peroxisome proliferator-activated receptor γ, adiponectin, and aP2. In addition, we also observed that IB induces lipogenic genes such as fatty acid synthase, sterol regulatory element binding protein 1c, stearoyl-CoA desaturase, and acetyl-CoA carboxylase. Interestingly IB regulated adipocyte differentiation in both the early and middle stages. Taken together, these adipogenic and lipogenic effects of IB suggest its efficacy for the prevention and/or treatment of type 2 diabetes.

scholarly journals Anti-Adipogenic Effects of Delphinidin-3-O-β-Glucoside in 3T3-L1 Preadipocytes and Primary White Adipocytes

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1848 ◽  
Author(s):  
Miey Park ◽  
Anshul Sharma ◽  
Hae-Jeung Lee
Keyword(s):  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Adenosine Monophosphate ◽  
Immunoblot Analysis ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
White Adipocytes ◽  
Health Promoting ◽  
Treatment Of Obesity

Delphinidin-3-O-β-glucoside (D3G) is a health-promoting anthocyanin whose anti-obesity activity has not yet been thoroughly investigated. We examined the effects of D3G on adipogenesis and lipogenesis in 3T3-L1 adipocytes and primary white adipocytes using real-time RT-PCR and immunoblot analysis. D3G significantly inhibited the accumulation of lipids in a dose-dependent manner without displaying cytotoxicity. In the 3T3-L1 adipocytes, D3G downregulated the expression of key adipogenic and lipogenic markers, which are known as peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element-binding transcription factor 1 (SREBP1), CCAAT/enhancer-binding protein alpha (C/EBPα), and fatty acid synthase (FAS). Moreover, the relative protein expression of silent mating type information regulation 2 homolog 1 (SIRT1) and carnitine palmitoyltransferase-1 (CPT-1) were increased, alongside reduced lipid levels and the presence of several small lipid droplets. Furthermore, D3G increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC), which suggests that D3G may play a role in AMPK and ACC activation in adipocytes. Our data indicate that D3G attenuates adipogenesis and promotes lipid metabolism by activating AMPK-mediated signaling, and, hence, could have a therapeutic role in the management and treatment of obesity.

scholarly journals LKB1 signalling attenuates early events of adipogenesis and responds to adipogenic cues

2014 ◽  
Vol 53 (1) ◽  
pp. 117-130 ◽  
Author(s):  
Amélie Gormand ◽  
Christine Berggreen ◽  
Lahouari Amar ◽  
Emma Henriksson ◽  
Ingrid Lund ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Histone Deacetylases ◽  
Fatty Acid Synthase ◽  
Nuclear Translocation ◽  
Adipogenic Differentiation ◽  
Camp Response Element Binding ◽  
Dominant Negative ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

cAMP-response element-binding protein (CREB) is required for the induction of adipogenic transcription factors such as CCAAT/enhancer-binding proteins (C/EBPs). Interestingly, it is known from studies in other tissues that LKB1 and its substrates AMP-activated protein kinase (AMPK) and salt-inducible kinases (SIKs) negatively regulate gene expression by phosphorylating the CREB co-activator CRTC2 and class IIa histone deacetylases (HDACs), which results in their exclusion from the nucleus where they co-activate or inhibit their targets. In this study, we show that AMPK/SIK signalling is acutely attenuated during adipogenic differentiation of 3T3-L1 preadipocytes, which coincides with the dephosphorylation and nuclear translocation of CRTC2 and HDAC4. When subjected to differentiation, 3T3-L1 preadipocytes in which the expression of LKB1 was stably reduced using shRNA (Lkb1-shRNA), as well as Lkb1-knockout mouse embryonic fibroblasts (Lkb1−/− MEFs), differentiated more readily into adipocyte-like cells and accumulated more triglycerides compared with scrambled-shRNA-expressing 3T3-L1 cells or Wt MEFs. In addition, the phosphorylation of CRTC2 and HDAC4 was reduced, and the mRNA expression of adipogenic transcription factors Cebpa, peroxisome proliferator-activated receptor γ (Pparg) and adipocyte-specific proteins such as hormone-sensitive lipase (HSL), fatty acid synthase (FAS), aP2, GLUT4 and adiponectin was increased in the absence of LKB1. The mRNA and protein expression of Ddit3/CHOP10, a dominant-negative member of the C/EBP family, was reduced in Lkb1-shRNA-expressing cells, providing a potential mechanism for the up-regulation of Pparg and Cebpa expression. These results support the hypothesis that LKB1 signalling keeps preadipocytes in their non-differentiated form.

scholarly journals Gene expressions of de novo hepatic lipogenesis in feline hepatic lipidosis

2019 ◽  
Vol 22 (6) ◽  
pp. 500-505
Author(s):  
Chiara Valtolina ◽  
Joris H Robben ◽  
Monique E van Wolferen ◽  
Hedwig S Kruitwagen ◽  
Ronald J Corbee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acid ◽  
Liver Tissue ◽  
Fatty Acid Synthase ◽  
De Novo ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Hepatic Lipidosis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Objectives The aim of this study was to evaluate if de novo hepatic lipid synthesis contributes to fatty acid overload in the liver of cats with feline hepatic lipidosis (FHL). Methods Lipogenic gene expression of peroxisome proliferator-activated receptor-alpha ( PPAR-α), peroxisome proliferator-activated receptor-gamma ( PPAR-γ), fatty acid synthase ( FASN) and sterol regulatory element-binding factor ( SREBF1) were evaluated using quantitative RT-PCR in liver tissue of six cats with FHL and compared with the liver tissue of eight healthy cats. Results In liver tissue, PPAR-α, PPAR-γ and FASN mRNA expression levels were not significantly different ( P >0.12, P >0.89 and P >0.5, respectively) in the FHL group compared with the control group. SREBF1 gene expression was downregulated around 10-fold in the FHL group vs the control group ( P = 0.039). Conclusions and relevance The downregulation of SREBF1 in the liver tissue of cats with FHL does not support the hypothesis that de novo lipogenesis in the liver is an important pathway of fatty acid accumulation in FHL.

Antitumor effects of energy restriction-mimetic agents: thiazolidinediones

2013 ◽  
Vol 394 (7) ◽  
pp. 865-870 ◽  
Author(s):  
Hany A. Omar ◽  
Samir A. Salama ◽  
El-Shaimaa A. Arafa ◽  
Jing-Ru Weng
Keyword(s):  
Glucose Transporter ◽  
Adenosine Monophosphate ◽  
Energy Restriction ◽  
Hypoglycemic Agents ◽  
Peroxisome Proliferator ◽  
Oral Hypoglycemic Agents ◽  
Antitumor Effects ◽  
Peroxisome Proliferator Activated Receptor ◽  
Novel Approach ◽  
Metabolic Strategies

Abstract Distinct metabolic strategies used by cancer cells to gain growth advantages, such as shifting from oxidative phosphorylation to glycolysis, constitute a basis for their selective targeting as a novel approach for cancer therapy. Thiazolidinediones (TZDs) are ligands for the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and they are clinically used as oral hypoglycemic agents. Accumulating evidence suggests that the ability of TZDs to suppress cancer cell proliferation through the interplay between apoptosis and autophagy was, at least in part, mediated through PPARγ-independent mechanisms. This review highlights recent advances in the pharmacological exploitation of the PPARγ-independent anticancer effects of TZDs to develop novel agents targeting tumor metabolism, including glucose transporter inhibitors and adenosine monophosphate-activated protein kinase, which have translational potential as cancer therapeutic agents.

scholarly journals Nigella Sativa and Ginger Increase GLUT4 and PPARγ in Metabolic Syndrome‐Induced Rats

2021 ◽  
Vol 11 (1) ◽  
pp. 3261-3269
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Glucose Transporter ◽  
Nigella Sativa ◽  
Body Weight Gain ◽  
Male Rats ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Increased fructose intake has been linked to the epidemiology of insulin resistance, type 2 diabetes mellitus, renal damage, and metabolic syndrome (MS). As oxidative stress plays a pivotal role in the pathology of insulin resistance, the present study was conducted to investigate the effects of Nigella Sativa (NS) and ginger as potent antioxidants on fructose-induced MS in rats. Male rats were fed with a high‐fructose high-fat-fed diet for 8 weeks. By the end of the 8th week, rats were divided into four groups; one was left untreated (normal control) and MS control group was treated with saline. MS groups were given Nigella sativa (4 ml/kg) and ginger (500 mg/kg) daily for 4 weeks. Markers chosen for assessment included the effect on body weight gain, glucose, insulin, adiponectin levels, and lipid profile. Also, protein expressions were estimated by glucose transporter 4 (GLUT4) content and peroxisome proliferator‐activated receptor‐gamma (PPARγ). Nigella sativa and ginger ameliorated some manifestations of MS, including an increase in body weight, glucose, insulin level, and resistance. Besides, both drugs lowered insulin resistance, induced hyperlipidemia and increased adiponectin level. Drugs also increased GLUT4 and PPARγ protein expression compared with MS control group. Nigella sativa and ginger ameliorated parameters of MS via increased GLUT4 and PPARγ expression.

scholarly journals Shockwaves Suppress Adipocyte Differentiation via Decrease in PPARγ

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 166
Author(s):  
Wonkyoung Cho ◽  
SeoYeon Kim ◽  
Myeongsook Jeong ◽  
Young Mi Park
Keyword(s):  
Adipocyte Differentiation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Intracellular Camp ◽  
Peroxisome Proliferator ◽  
Mechanical Stimuli ◽  
Western Blots ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pparγ Expression ◽  
Camp Levels

Adipogenesis is a crucial cellular process that contributes to the expansion of adipose tissue in obesity. Shockwaves are mechanical stimuli that transmit signals to cause biological responses. The purpose of this study is to evaluate the effects of shockwaves on adipogenesis. We treated 3T3L-1 cells and human primary preadipocytes for differentiation with or without shockwaves. Western blots and quantitative real-time reverse transcriptase PCR (qRT-PCR) for adipocyte markers including peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT-enhancer-binding proteins (C/EBPα) were performed. Extracellular adenosine triphosphate (ATP) and intracellular cyclic adenosine monophosphate (cAMP) levels, which are known to affect adipocyte differentiation, were measured. Shockwave treatment decreased intracellular lipid droplet accumulation in primary human preadipocytes and 3T3-L1 cells after 11–12 days of differentiation. Levels of key adipogenic transcriptional factors PPARγ and/or C/EBPα were lower in shockwave-treated human primary preadipocytes and 3T3L-1 cells after 12–13 days of differentiation than in shockwave-untreated cells. Shockwave treatment induced release of extracellular ATP from preadipocytes and decreased intracellular cAMP levels. Shockwave-treated preadipocytes showed a higher level of β-catenin and less PPARγ expression than shockwave-untreated cells. Supplementation with 8-bromo-cAMP analog after shockwave treatment rescued adipocyte differentiation by preventing the effect of shockwaves on β-catenin, Wnt10b mRNA, and PPARγ expression. Low-energy shockwaves suppressed adipocyte differentiation by decreasing PPARγ. Our study suggests an insight into potential uses of shockwave-treatment for obesity.

scholarly journals Hypoxic Exposure Increases Energy Expenditure by Increasing Carbohydrate Oxidation in Mice

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yeram Park ◽  
Deunsol Hwang ◽  
Hun-Young Park ◽  
Jisu Kim ◽  
Kiwon Lim
Keyword(s):  
Glucose Metabolism ◽  
Energy Expenditure ◽  
Pyruvate Dehydrogenase ◽  
Hypoxic Condition ◽  
Open Circuit ◽  
Pyruvate Dehydrogenase Kinase ◽  
Hypoxic Exposure ◽  
Control Group ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Aims. Hypoxic exposure improves glucose metabolism. We investigated to validate the hypothesis that carbohydrate (CHO) oxidation could increase in mice exposed to severe hypoxic conditions. Methods. Seven-week-old male ICR mice (n=16) were randomly divided into two groups: the control group (CON) was kept in normoxic condition (fraction of inspired O2=21%) and the hypoxia group (HYP) was exposed to hypoxic condition (fraction of inspired O2=12%, ≈altitude of 4,300 m). The CON group was pair-fed with the HYP group. After 3 weeks of hypoxic exposure, we measured respiratory metabolism (energy expenditure and substrate utilization) at normoxic conditions for 24 hours using an open-circuit calorimetry system. In addition, we investigated changes in carbohydrate mechanism-related protein expression, including hexokinase 2 (HK2), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), and regulator of the genes involved in energy metabolism (peroxisome proliferator-activated receptor gamma coactivator 1-alpha, PGC1α) in soleus muscle. Results. Energy expenditure (EE) and CHO oxidation over 24 hours were higher in the HYP group by approximately 15% and 34% (p<0.001), respectively. Fat oxidation was approximately 29% lower in the HYP group than the CON group (p<0.01). Body weight gains were significantly lower in the HYP group than in the CON group (CON vs. HYP; 1.9±0.9 vs. −0.3±0.9; p<0.001). Hypoxic exposure for 3 weeks significantly reduced body fat by approximately 42% (p<0.001). PDH and PGC1α protein levels were significantly higher in the HYP group (p<0.05). Additionally, HK2 was approximately 21% higher in the HYP group. Conclusions. Hypoxic exposure might significantly enhance CHO oxidation by increasing the expression of PDH and HK2. This investigation can be useful for patients with impaired glucose metabolism, such as those with type 2 diabetes.

scholarly journals The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1025
Author(s):  
Ahmed Alalaiwe ◽  
Jia-You Fang ◽  
Hsien-Ju Lee ◽  
Chun-Hui Chiu ◽  
Ching-Yun Hsu
Keyword(s):  
Molecular Docking ◽  
Fatty Acid Synthase ◽  
Structural Similarity ◽  
Mechanistic Study ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Enhancer Binding Protein ◽  
Underlying Mechanisms ◽  
Amp Activated Protein Kinase

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 μM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 μM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

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