Adipogenesis-related Transcription Factors Research Articles

Thiacremonone, a sulfur compound isolated from garlic, attenuates lipid accumulation partially mediated via AMPK activation in 3T3-L1 adipocytes

Garlic extracts exert anti-cancer and anti-inflammatory effects. However, the anti-adipogenic effect of garlic-derived compounds remains unclear. In this study, we examined the effect of thiacremonone, a sulfur compound isolated from garlic, on adipocyte differentiation using 3T3-L1 cells. We found that thiacremonone significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation in 3T3-L1 cells. There was no cytotoxic effect of thiacremonone in 3T3-L1 cells and treatment of differentiating 3T3-L1 cells with thiacremonone resulted in AMPK activation, which led to an attenuated expression of acetyl CoA carboxylase-1 (ACC-1), an essential enzyme for the synthesis and usage of fatty acids. Moreover, thiacremonone enhanced the mRNA level of carnitine palmitoyltransferase (CPT-1). The modulating effect of thiacremonone on expressions of genes involved in lipolysis was partially abrogated by treatment with compound C, an AMPK inhibitor. Taken together, these results indicated that thiacremonone-induced AMPK activation, inhibition of ACC-1 expression and concomitant recovery of CPT-1 expression resulted in the suppression of intracellular lipid droplet levels, suggesting that thiacremonone may induce reduction of lipid synthesis and increases in fatty acid oxidation partially mediated via AMPK activation. Thiacremonone may be a promising compound for the treatment of obesity.

Differentiation of human adipose-derived stem cells induced by recombinantly expressed fibroblast growth factor 10 in vitro and in vivo

The adipogenesis effect of fibroblast growth factor 10 (FGF10) has been demonstrated in many studies. The aim of this study is to render a novel method which can continuously induce hypodermal adipose-derived stem cell (ADSC) differentiation and maturation in vivo and in vitro using FGF10. We constructed a recombinant pcDNA3.0-FGF10-MSC which can continuously express FGF10 by transfected FGF10 into a human mesenchymal stem cell (MSC) clone, and we cultured ADSCs from human subcutaneous resected adipose tissue. An in vitro and in vivo coculture system of pcDNA3.0-FGF10-MSC and ADSCs was then established. We observed the characteristics of ADSCs, monitored the adipogenesis-related transcription factor CAAT/enhancer binding protein-β, peroxisome proliferator-activated receptor-γ, and measured the adipose tissue layer of carrier animals. The results showed that FGF10 secreted from pcDNA3.0-FGF10-MSC could induce ADSC differentiation into mature adipocytes consistently. The study demonstrated that FGF10 can promote the adipogenesis effect in situ, and the autotransplantation of a carrier continuously secreting FGF10 may be utilized for increasing local subcutaneous adipose tissue in cosmetology.

White Tea extract induces lipolytic activity and inhibits adipogenesis in human subcutaneous (pre)-adipocytes

BackgroundThe dramatic increase in obesity-related diseases emphasizes the need to elucidate the cellular and molecular mechanisms underlying fat metabolism. To investigate how natural substances influence lipolysis and adipogenesis, we determined the effects of White Tea extract on cultured human subcutaneous preadipocytes and adipocytes.MethodsFor our in vitro studies we used a White Tea extract solution that contained polyphenols and methylxanthines. Utilizing cultured human preadipocytes we investigated White Tea extract solution-induced inhibition of triglyceride incorporation during adipogenesis and possible effects on cell viability. In vitro studies on human adipocytes were performed aiming to elucidate the efficacy of White Tea extract solution to stimulate lipolytic activity. To characterize White Tea extract solution-mediated effects on a molecular level, we analyzed gene expression of essential adipogenesis-related transcription factors by qRT-PCR and determined the expression of the transcription factor ADD1/SREBP-1c on the protein level utilizing immunofluorescence analysis.ResultsOur data show that incubation of preadipocytes with White Tea extract solution significantly decreased triglyceride incorporation during adipogenesis in a dose-dependent manner (n = 10) without affecting cell viability (n = 10). These effects were, at least in part, mediated by EGCG (n = 10, 50 μM). In addition, White Tea extract solution also stimulated lipolytic activity in adipocytes (n = 7). Differentiating preadipocytes cultivated in the presence of 0.5% White Tea extract solution showed a decrease in PPARγ, ADD1/SREBP-1c, C/EBPα and C/EBPδ mRNA levels. Moreover, the expression of the transcription factor ADD1/SREBP-1c was not only decreased on the mRNA but also on the protein level.ConclusionWhite Tea extract is a natural source that effectively inhibits adipogenesis and stimulates lipolysis-activity. Therefore, it can be utilized to modulate different levels of the adipocyte life cycle.

Inhibitory Effects of A-769662, a Novel Activator of AMP-Activated Protein Kinase, on 3T3-L1 Adipogenesis

AMP-activated protein kinase (AMPK) is a central player in glucose and lipid metabolism while its role in adipocyte differentiation remains obscure. A-769662, a novel activator of AMPK, has been implicated to reduce body weight gain and decrease liver and plasma triglyceride levels via increasing fatty acid oxidation and reducing fatty acid synthesis in vivo. In this study, we examined the effects of A-769662 on adipocyte differentiation using 3T3-L1 cells. We found that A-769662 significantly inhibited 3T3-L1 differentiation via down-regulation of adipogenesis-related transcription factors and adipogenic markers. The inhibitory effect mainly occurred at the early phase of differentiation through inhibition of mitotic clonal expansion (MCE), which was essential for adipogenesis. A-769662 also decreased cell viability of differentiating and mature 3T3-L1 adipocytes. Moreover, treatment of differentiating 3T3-L1 cells with A-769662 resulted in AMPK over-activation, which led to an increased phosphorylation and inactivation of acetyl-CoA carboxylase (ACC), an important enzyme for the synthesis and usage of fatty acids. Taken together, these results suggest that A-769662 inhibits 3T3-L1 adipogenic differentiation in several ways and therefore may be a promising compound for the treatment of obesity.

Berberine inhibits 3T3-L1 adipocyte differentiation through the PPARγ pathway

Berberine (BBR), a compound purified from Cortidis rhizoma, reduces serum cholesterol, triglycerides, and LDL-cholesterol of hypercholesterolemic patients and high fat diet fed animals, and increases hepatic LDLR mRNA and protein levels through a post-transcriptional mechanism. BBR also enhances the hypoglycemic action of insulin in diabetic animal models. Here, we show that BBR inhibits the differentiation of 3T3-L1 preadipocytes induced by DM and suppresses the mitotic clonal expansion of 3T3-L1 preadipocytes in a time- and dose-dependent manner. Gene expression analysis and Western blot analysis reveal that the BBR inhibits the mRNA and protein levels of adipogenesis related transcription factors PPARγ and C/EBPα and their upstream regulator, C/EBPβ. Reporter gene assays demonstrate that the full-length PPARγ and α transcription activities are inhibited by BBR. Using real-time PCR, we have also found that the PPAR target genes that are involved in adipocyte differentiation, such as aP2, CD36, ACO, LPL, and other adipocyte markers, are suppressed by BBR. These studies suggest that BBR works on multiple molecular targets as an inhibitor of PPARγ and α, and is a potential weight reducing, hypolipidemic, and hypoglycemic drug.

Anti‐obesity actions of green tea: Possible involvements in modulation of the glucose uptake system and suppression of the adipogenesis‐related transcription factors

To investigate mechanisms of the anti-obesity actions of green tea in vivo, rats were given green tea instead of drinking water for 3 weeks. It was confirmed that green tea reduced adipose tissue weight without any change in body weight, other tissue weights, and food and water intakes. Green tea also significantly reduced the plasma levels of cholesterols and free fatty acids. Certain catechins existed in the plasma at 0.24 microM under our experimental conditions, though most of them existed as conjugated forms. For mechanisms of the anti-obesity actions, green tea significantly reduced glucose uptake accompanied by a decrease in translocation of glucose transporter 4 (GLUT4) in adipose tissue, while it significantly stimulated the glucose uptake with GLUT4 translocation in skeletal muscle. Moreover, green tea suppressed the expression of peroxisome proliferator-activated receptor gamma and the activation of sterol regulatory element binding protein-1 in adipose tissue. In conclusion, green tea modulates the glucose uptake system in adipose tissue and skeletal muscle and suppresses the expression and/or activation of adipogenesis-related transcription factors, as the possible mechanisms of its anti-obesity actions.