• The Korean Journal of Physiology and Pharmacology
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• v.23 no.3
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• pp.161-169
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• 2019

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

• Korean Journal of Food Science and Technology
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• v.53 no.2
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• pp.149-153
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• 2021

Mandarin peel (MP) is a by-product of the processing of citrus juice or other products. This study aimed to investigate the potential anti-obesity effect of an enzymatic extract of MP on the inhibition of adipogenesis in 3T3-L1 adipocytes. The enzymatic extract (MPCE) was prepared using the commercial food-grade carbohydrase Celluclast. Lipid accumulation and triglyceride levels were significantly lower in MPCE-treated cells than in untreated cells. In addition, MPCE treatment reduced the protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding protein α, sterol regulatory element-binding protein 1, and fatty acid-binding protein 4. These results suggest that MPCE inhibits adipogenesis by downregulating the expression levels of adipogenesis-related proteins. Therefore, the current findings demonstrate that MPCE possesses potent anti-obesity properties and could be a potential ingredient in functional food industries.

• International Journal of Molecular Medicine
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• v.45 no.2
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• pp.589-596
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• 2020

Acer okamotoanum is reported to have various antioxidant, anti-inflammatory and beneficial immune system effects. The anti-adipocyte differentiation effects and mechanisms of the ethyl acetate (EtOAc) fraction of an A. okamotoanum extraction was investigated in 3T3-L1 adipocyte cells. Treatment with differentiation inducers increased the level of triglycerides (TGs) in 3T3-L1 adipocyte cells compared with an untreated control. However, the EtOAc fraction of A. okamotoanum significantly decreased TGs. Treatment with 1, 2.5 and 5 ㎍/ml showed weak activity, but TG production was inhibited at 10 ㎍/ml compared with the control. In addition, A. okamotoanum caused a significant downregulation of proteins related to adipogenesis, such as γ-cytidine-cytidine-adenosine-adenosine-thymidine/enhancer binding protein-α, -β and peroxisome proliferator-activated receptor-γ, compared with the untreated control. Furthermore, A. okamotoanum significantly upregulated lipolysis related protein, hormone-sensitive lipase and the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Therefore, these results indicate that A. okamotoanum suppressed adipogenesis and increased lipolysis and the activation of AMPK, suggesting a protective role in adipocyte differentiation.

• Journal of Web Engineering
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• v.14 no.18
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• pp.3814-3828
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• 2022

Glucoraphanin (GRA), a glucosinolate particularly abundant in broccoli (Brassica oleracea var. italica) sprouts, can be converted to sulforaphane (SFN) by the enzyme myrosinase. Herein, we investigated the anti-obesogenic effects of broccoli sprout powder (BSP), mustard (Sinapis alba L.) seed powder (MSP), and sulforaphane-rich MSP-BSP mixture powder (MBP) in bisphenol A (BPA)-induced 3T3-L1 cells and obese C57BL/6J mice. In vitro experiments showed that MBP, BSP, and MSP have no cytotoxic effects. Moreover, MBP and BSP inhibited the lipid accumulation in BPA-induced 3T3-L1 cells. In BPA-induced obese mice, BSP and MBP treatment inhibited body weight gain and ameliorated dyslipidemia. Furthermore, our results showed that BSP and MBP could activate AMPK, which increases ACC phosphorylation, accompanied by the upregulation of lipolysis-associated proteins (UCP-1 and CPT-1) and downregulation of adipogenesis-related proteins (C/EBP-α, FAS, aP2, PPAR-γ, and SREBP-1c), both in vitro and in vivo. Interestingly, MBP exerted a greater anti-obesogenic effect than BSP. Taken together, these findings indicate that BSP and MBP could inhibit BPA-induced adipocyte differentiation and adipogenesis by increasing the expression of the proteins related to lipid metabolism and lipolysis, effectively treating BPA-induced obesity. Thus, BSP and MBP can be developed as effective anti-obesogenic drugs.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.444-455
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• 2021

BACKGROUND/OBJECTIVES: Adipocytes undergo angiogenesis to receive nutrients and oxygen needed for adipocyte' growth and differentiation. No study relating quercetin with angiogenesis in adipocytes exists. Therefore, this study investigated the role of quercetin on adipogenesis in 3T3-L1 cells, acting through matrix metalloproteinases (MMPs). MATERIALS/METHODS: After proliferating preadipocytes into adipocytes, various quercetin concentrations were added to adipocytes, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to evaluate cell proliferation. Glycerol-3-phosphate dehydrogenase (GPDH) activity was investigated as an indicator of fat accumulation. The mRNA expressions of transcription factors related to adipocyte differentiation, CCAAT/enhancer-binding proteins (C/EBPs), peroxisomal proliferatoractivated receptors (PPAR)-γ, and adipocyte protein 2 (aP2), were investigated. The mRNA expressions of proteins related to angiogenesis, vascular endothelial growth factor (VEGF)-α, vascular endothelial growth factor receptor (VEGFR)-2, MMP-2, and MMP-9, were investigated. Enzyme activities and concentrations of MMP-2 and MMP-9 were also measured. RESULTS: Quercetin treatment suppressed fat accumulation and the expressions of adipocyte differentiation-related genes (C/EBPα, C/EBPβ, PPAR-γ, and aP2) in a concentration-dependent manner in 3T3-L1 cells. Quercetin treatments reduced the mRNA expressions of VEGF-α, VEGFR-2, MMP-2, and MMP-9 in 3T3-L1 cells. The activities and concentrations of MMP-2 and MMP-9 were also decreased significantly as the concentration of quercetin increased. CONCLUSIONS: The results confirm that quercetin inhibits adipose tissue differentiation and fat accumulation in 3T3-L1 cells, which could occur through inhibition of the angiogenesis process related to MMPs.

• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.3
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• pp.288-295
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• 2014

Bojungchiseub-tang (BJCST) has been used in symptoms and signs of edema, dampness-phlegm, kidney failure, and so on. BJCST is also expected to have strong anti-obesity activities. However, little is known about the mechanisms of its inhibitory effects on adipocyte differentiation and adipogenesis. In the present study, we examined the effects and mechanism of BJCST on transcription factors and adipogenic genes of 3T3-L1 preadipocytes to understand its inhibitory effects on adipocyte differentiation and adipogenesis. Our results showed that BJCST significantly inhibited differentiation and adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner. To elucidate the mechanism of the effects of BJCST on lowering lipid content in 3T3-L1 adipocytes, we examined whether BJCST modulate the expressions of transcription factors to induce adipogenesis and adipogenic genes related to regulate accumulation of lipids. As a result, the expression of steroid regulatory element-binding protein (SREBP)1, cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ ($C/EBP{\alpha}$), $C/EBP{\beta}$, $C/EBP{\delta}$, and peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) genes, which induce the adipose differentiation, liver X receptor $(LXR){\alpha}$ and fatty acid synthase (FAS) genes, which induce lipogenesis and adipose-specific aP2, Adipsin, lipoprotein lipase (LPL), CD36, TGF-${\beta}$, leptin and adiponectin genes, which compose fat formation were decreased. BJCST also reduced the expression of acyl CoA oxidase (ACO) and uncoupling protein (UCP) genes related to lipid oxidation. In conclusion, BJCST could regulate transcript factor related to induction of adipose differentiation and inhibited the accumulation of lipids and expression of adipogenic genes.

• Journal of Korean Medicine for Obesity Research
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• v.22 no.1
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• pp.30-37
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• 2022

Objectives: Adipogenesis is the process by which pre-adipocytes are differentiated into adipocytes. It also plays an important role in adipocyte formation and lipid accumulation. Ranunculus sceleratus (R. sceleratus) extracts are used for the treatment of various diseases such as hepatitis, jaundice, and tuberous lymphadenitis in oriental medicine. However, its effect on adipogenesis has not yet been studied. In this study, we investigated the effects of R. sceleratus on adipogenesis in 3T3-L1 cells. Methods: Cells were treated with 50, 100, and 200 ㎍/ml of R. sceleratus and cell viability was evaluated. To differentiate the 3T3-L1 preadipocytes, a 3-isobutyl-1-methylxanthine, dexamethasone, and insulin (MDI) solution were used. The accumulation of lipid droplets was determined by Oil Red O staining. The expression levels of adipogenesis-related proteins were also determined. Results: MDI solution differentiated the preadipocytes into adipocytes and accumulation of lipids was observed in the differentiated 3T3-L1 cells. Interestingly, the amount of lipid droplets was reduced after R. sceleratus treatment. In addition, the expression levels of key adipogenic transcription factors, such as CCAAT/enhancer-binding proteins-𝛼 (C/EBP-𝛼) and peroxisome proliferator-activated receptors-𝛾 (PPAR-𝛾) were also reduced after R. sceleratus treatment. Furthermore, R. sceleratus increased AMP-activated kinase (AMPK) phosphorylation and decreased sterol regulatory element-binding protein-1 expression. Conclusions: Our results showed that R. sceleratus reduced preadipocyte differentiation by inhibiting C/EBP-𝛼 and PPAR-𝛾 levels via the AMPK pathway. Therefore, we suggest that R. sceleratus may be potentially used as an anti-adipogenic agent.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.186-196
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• 2023

Dyglomera^® is an aqueous ethanol extract derived from the fruit and pods of Dichrostachys glomerata. A previous study has revealed that Dyglomera regulates adipogenesis and lipolysis by modulating AMP-activated protein kinase (AMPK) phosphorylation and increased expression levels of lipolysis-related proteins in white adipose tissue of high fat diet-induced mice and 3T3-L1 adipocyte cells. To further investigate mechanisms of Dyglomera, additional studies were performed using 3T3-L1 cells. Results revealed that Dyglomera downregulated adipogenesis by inhibiting the protein kinase B/mammalian target of rapamycin signaling pathway and reconfirmed that it downregulated gene expression levels of proliferator-activated receptor (PPAR)-γ, CCAAT enhancer binding protein α, sterol-regulation element-binding protein-1c. Dyglomera also reduced adipokines such as tumor necrosis factor alpha, interleukin-1β, and interleukin 6 by regulating leptin expression. Moreover, Dyglomera promoted beige-and-brown adipocyte-related phenotypes and regulated metabolism by increasing mitochondrial number and expression levels of genes such as T-box protein 1, transmembrane protein 26, PR domain 16, and cluster of differentiation 40 as well as thermogenic factors such as uncoupling protein 1, proliferator-activated receptor-gamma co-activator-1α, Sirtuin 1, and PPARα through AMPK activation. Thus, Dyglomera not only can inhibit adipogenesis, but also can promote lipolysis and thermogenesis and regulate metabolism by affecting adipokine secretion from 3T3-L1 adipocytes.

• Journal of Physiology & Pathology in Korean Medicine
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• v.34 no.3
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• pp.136-141
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• 2020

The purpose of this study was to investigate the action mechanism of the roots of Adenophora triphylla var. japonica extract (ATE) in 3T3-L1 adipocytes. Cell toxicity test by MTT assay and lipid accumulation was performed to evaluate the inhibitory effect on the differentiation of adipocyte from preadipocytes induced by MDI differentiation medium, while adipogenesis related proteins expression level were evaluated by western blotting. As a result, ATE inhibited MDI-induced adipocyte differentiation in 3T3-L1 cells dose-dependently without cytotoxicity. Our results showed that ATE inhibited the phosphorylation of IRS1, thereby decreasing the expression of PI3K110α and reducing the phosphorylation of AKT and mTOR, resulting in attenuated protein expression of C/EBPα, PPARγ, ap2 and FAS in 3T3-L1 cells. These results suggest anti-adipogenic functions for ATE, and identified IRS1 as a novel target for ATE in adipogenesis.

• Journal of Applied Biological Chemistry
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• v.59 no.1
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• pp.49-56
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• 2016

The current study investigated the anti-obesity effect of Cissus quadrangularsis extracts (CQR-300) and its molecular action mechanism on obese mice induced high-fat diet (HFD). To induce the obesity, mice were fed a HFD for 6 weeks and then fed HFD only or HFD with CQR-300 at 50 and 200 mg/kg. Then, body weight gain and white adipose tissue weights were measured. We investigated the reduction in body fat and the regulation of fatty acid synthesis was measured by dual energy X-ray absorptiometry and real-time PCR with Western blot, respectively. In vitro study, CQR-300 inhibited pancreatic lipase activity. The CQR-300 treatment was significantly decreased the body weight gain and adipocytes size as well as white adipose tissues weights in HFD-induced obese mice. Furthermore, CQR-300 reduced the body fat and fat mass with regulating of adipose tissue hormones as leptin. Treatment with 50 mg/kg CQR-300 showed effectively lower expression levels of adipogenesis/lipogenesis related genes and proteins such as CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), Sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) in white adipose tissue (WAT) as compared with the HFD fed only mice. These results suggest that the CQR-300 has an anti-obesity effect via inhibition of lipase activity, decrease the body fat mass by regulating the adipogenesis and lipogenesis related genes and proteins in epididymal adipose tissue with evaluate body fat reduce in the HFD-induced obese mice.