scholarly journals miR-135a-5p inhibits 3T3-L1 adipogenesis through activation of canonical Wnt/β-catenin signaling

2014 ◽  
Vol 52 (3) ◽  
pp. 311-320 ◽  
Author(s):  
Chen Chen ◽  
Yongdong Peng ◽  
Yinglin Peng ◽  
Jian Peng ◽  
Siwen Jiang
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Adipogenic Differentiation ◽  
Transcriptional Regulators ◽  
Marker Genes ◽  
Preadipocyte Differentiation ◽  
Fatty Acid Binding ◽  
Canonical Wnt ◽  
Adipogenic Marker

MicroRNAs are endogenous, conserved, and non-coding small RNAs that function as post-transcriptional regulators of fat development and adipogenesis. Adipogenic marker genes, such as CCAAT/enhancer binding protein α (Cebpa), peroxisome proliferator-activated receptor γ (Pparg), adipocyte fatty acid binding protein (Ap2), and fatty acid synthase (Fas), are regarded as the essential transcriptional regulators of preadipocyte differentiation and lipid storage in mature adipocytes. Canonical Wnt/β-catenin signaling is recognized as a negative molecular switch during adipogenesis. In the present work we found that miR-135a-5p is markedly downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-135a-5p impairs the expressions of adipogenic marker genes as well as lipid droplet accumulation and triglyceride content, indicating the importance of miR-135a-5p for adipogenic differentiation and adipogenesis. Further studies show that miR-135a-5p directly targets adenomatous polyposis coli (Apc), contributes to the translocation of β-catenin from cytoplasm to nucleus, and then activates the expressions of cyclin D1 (Ccnd1) and Cmyc, indicating the induction of canonical Wnt/β-catenin signaling. In addition, inhibition of APC with siRNA exhibits the same effects as overexpression of miR-135a-5p. Our findings demonstrate that miR-135a-5p suppresses 3T3-L1 preadipocyte differentiation and adipogenesis through the activation of canonical Wnt/β-catenin signaling by directly targeting Apc. Taken together, these results offer profound insights into the adipogenesis mechanism and the development of adipose tissue.

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

2018 ◽  
Vol 46 (01) ◽  
pp. 107-118 ◽  
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.

scholarly journals Bta-miR-34b regulates milk fat biosynthesis by targeting mRNA decapping enzyme 1A (DCP1A) in cultured bovine mammary epithelial cells1

2019 ◽  
Vol 97 (9) ◽  
pp. 3823-3831 ◽  
Author(s):  
Yujuan Wang ◽  
Wenli Guo ◽  
Keqiong Tang ◽  
Yaning Wang ◽  
Linsen Zan ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Droplet ◽  
Milk Fat ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Mammary Epithelial ◽  
Luciferase Reporter ◽  
Fatty Acid Binding ◽  
Fat Synthesis ◽  
Milk Fat Synthesis

Abstract Milk fat is a main nutritional component of milk, and it has become one of the important traits of dairy cow breeding. Recently, there is increasing evidence that microRNAs (miRNA) play significant roles in the process of milk fat synthesis in the mammary gland. Primary bovine mammary epithelial cells (BMEC) were harvested from midlactation cows and cultured in DMEM/F-12 medium with 10% fetal bovine serum, 100 units/mL penicillin, 100 µg/mL streptomycin, 5 µg/mL bovine insulin, 1 µg/mL hydrocortisone, and 2 µg/mL bovine prolactin. We found that miR-34b mimic transfection in BMEC reduced the content of intracellular triacylglycerol (TAG) and lipid droplet accumulation via triacylglycerol assay and Oil Red O staining; meanwhile, overexpression of miR-34b inhibited mRNA expression of lipid metabolism-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), and CCAAT enhancer binding protein alpha (C/EBPα). Whereas miR-34b inhibitor resulted in completely opposite results. Furthermore, q-PCR and western blot analysis revealed the mRNA and protein expression levels of DCP1A were downregulated in miR-34b mimic transfection group and upregulated in miR-34b inhibitor group. Moreover, luciferase reporter assays verified that DCP1A was the direct target of miR-34b and DCP1A gene silencing in BMEC-inhibited TAG accumulation and suppressed lipid droplet formation. In conclusion, these findings revealed a novel miR-34b–DCP1A axis that has a significant role in regulating milk fat synthesis and suggested that miR-34b may be used to improve the beneficial ingredients in milk.

Dietary threonine supplementation improves hepatic lipid metabolism of Pekin ducks

2019 ◽  
Vol 59 (4) ◽  
pp. 673 ◽  
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.

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 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.

Lipin1-Mediated Repression of Adipogenesis by Rutin

2016 ◽  
Vol 44 (03) ◽  
pp. 565-578 ◽  
Author(s):  
Yo-Han Han ◽  
Ji-Ye Kee ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Soyoung Shin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Related Factors ◽  
Fatty Acid Binding ◽  
Upstream Regulator ◽  
Enhancer Binding Protein ◽  
Adipogenic Effect

Rutin, also called rutoside or quercetin-3-O-rutinoside and sophorin, is a glycoside between the flavonol quercetin and the disaccharide rutinose. Although many effects of rutin have been reported in vitro and in vivo, the anti-adipogenic effects of rutin have not been fully reported. The aim of this study was to confirm how rutin regulates adipocyte related factors. In this study, rutin decreased the expressions of adipogenesis-related genes, including peroxisome proliferators, activated receptor [Formula: see text] (PPAR[Formula: see text], CCAAT/enhancer-binding protein [Formula: see text] (C/EBP[Formula: see text], fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase in 3T3-L1 cells. Rutin also repressed the expression of lipin1, which is an upstream regulator that controls PPAR[Formula: see text] and C/EBP[Formula: see text]. In addition, when 3T3-L1 was transfected with lipin1 siRNA to block lipin1 function, rutin did not affect the expressions of PPAR[Formula: see text] and C/EBP[Formula: see text]. These results suggest that rutin has an anti-adipogenic effect that acts through the suppression of lipin1, as well as PPAR[Formula: see text] and C/EBP[Formula: see text].

Bergamottin Inhibits Adipogenesis in 3T3-L1 Cells and Weight Regulation in Diet-Induced Obese Mice

2018 ◽  
Vol 46 (03) ◽  
pp. 601-615 ◽  
Author(s):  
Jeong-Hyeon Ko ◽  
Dongwoo Nam ◽  
Jae-Young Um ◽  
Sang Hoon Jung ◽  
Kwang Seok Ahn
Keyword(s):  
Binding Protein ◽  
Adipogenic Differentiation ◽  
Physiological Role ◽  
Brown Adipocyte ◽  
Marker Genes ◽  
Obese Mouse ◽  
Peroxisome Proliferator ◽  
Ampk Activation ◽  
Obese Mice ◽  
Fatty Acid Binding

Obesity is a serious and increasing health problem worldwide, and the inhibition of adipogenesis is considered to be a potential therapeutic target for it. Bergamottin (BGM), a component of grapefruit juice, has been reported to regulate lipolysis. However, the physiological role of BGM in obesity has not been evaluated so far. In the present study, we investigated the effects of BGM on obesity in 3T3-L1 cells and in mice fed a high-fat diet (HFD). BGM inhibited adipogenic differentiation of 3T3-L1 cells along with a significant decrease in the lipid content by downregulating the expression of two critical adipogenic factors, CCAAT enhancer-binding protein-alpha (C/EBP[Formula: see text]) and peroxisome proliferator activated receptor-gamma (PPAR[Formula: see text]). The expressions of target proteins such as adipocyte fatty acid-binding protein (aP2), adiponectin, and resistin were also decreased by BGM. It activated AMP-activated protein kinase (AMPK) by increasing phosphorylation of AMPK and the downstream target acetyl-CoA carboxylase (ACC), indicating that BGM exerted its antiadipogenic effect through AMPK activation. In the HFD-induced obese mouse model, BGM administration significantly reduced the weight and sizes of white adipose tissue as well as the weight gain of mice fed HFD. Moreover, UCP1 and PGC1[Formula: see text] expressions, well-known as brown adipocyte marker genes, were higher in the BGM-treated HFD mice than that in the HFD-induced obese mice. This study suggests that BGM suppress adipogenesis by AMPK activation in vitro and reduces body weight in vivo.

scholarly journals How Does Ginsenoside Rh2 Mitigate Adipogenesis in Cultured Cells and Obese Mice?

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2412
Author(s):  
Longyun Zhang ◽  
Carlos Virgous ◽  
Hongwei Si
Keyword(s):  
Fatty Acid ◽  
Cell Differentiation ◽  
Fatty Acid Synthase ◽  
Binding Protein ◽  
Ginsenoside Rh2 ◽  
Obese Mice ◽  
Fatty Acid Binding ◽  
Ppar Γ ◽  
In Cells

Ginsenoside Rh2, an intermediate metabolite of ginseng, but not naturally occurring, has recently drawn attention because of its anticancer effect. However, it is not clear if and how Rh2 inhibits preadipocytes differentiation. In the present study, we hypothesized that ginsenoside Rh2 attenuates adipogenesis through regulating the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway both in cells and obese mice. Different concentrations of Rh2 were applied both in 3T3-L1 cells and human primary preadipocytes to determine if Rh2 inhibits cell differentiation. Dietary Rh2 was administered to obese mice to determine if Rh2 prevents obesity in vivo. The mRNA and protein expression of PPAR-γ pathway molecules in cells and tissues were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Our results show that Rh2 dose-dependently (30–60 μM) inhibited cell differentiation in 3T3-L1 cells (44.5% ± 7.8% of control at 60 μM). This inhibitory effect is accompanied by the attenuation of the protein and/or mRNA expression of adipogenic markers including PPAR-γ and CCAAT/enhancer binding protein alpha, fatty acid synthase, fatty acid binding protein 4, and perilipin significantly (p < 0.05). Moreover, Rh2 significantly (p < 0.05) inhibited differentiation in human primary preadipocytes at much lower concentrations (5–15 μM). Furthermore, dietary intake of Rh2 (0.1 g Rh2/kg diet, w/w for eight weeks) significantly (p < 0.05) reduced protein PPAR-γ expression in liver and hepatic glutathione reductase and lowered fasting blood glucose. These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway, and Rh2 may be a potential agent in preventing obesity in vivo.

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