• Journal of Life Science
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• v.21 no.3
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• pp.358-367
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• 2011

Soybean is known to contain various phytochemicals that are related to anti-oxidant, anti-inflammatory and anti-obesity effects in mice and humans. The anti-obesity effect of by-product extracts from soybean on the differentiation of 3T3-L1 pre-adipocytes to adipocytes was investigated by suppressing adipocyte differentiation and lipid accumulation with Oil Red-O assay and quantitative PCR. In inducing differentiation of 3T3-L1 pre-adipocytes in the presence of an adipogenic cocktail, isobutylmethylanthine (IBMX), dexamathasone, and insulin, treatment with filtrated soybean soaked water, soybean milk, and soycurd residue from soybean curd processing significantly decreased mRNA expression of obesity-related gene such as PPAR${\gamma}$, Fabp4, and Scd1, adipsin, apolipoprotein (APOE) and adiponectin (ADIPOQ) without any significant cytotoxicity. We also determined the well-known isoflavones in soybean, such as daidzein and genistein, in the by-product extracts. Taken together, we suggest that soybean by-product extract showed anti-obesity effect by suppressing adipocyte related gene expression, and that by-products collected during soybean curd processing may be a good candidate as an ingredient in health care products.

• CELLMED
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• v.8 no.3
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• pp.11.1-11.6
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• 2018

In vitro anti-obesity effects of anti-cancer (AC) functional kimchi in differentiated 3T3-L1 adipocytes were studied. We constructed three experimental groups: Control, standardized kimchi (SK), and AC functional kimchi (A-FK) that included active ingredients and Lactobacillus plantarum. Kimchi extracts did not show any cytotoxicity in pre-adipocytes in the concentration range of 1 - 5 mg/mL. A-FK significantly reduced fat droplet formation and absorbance in differentiated 3T3-L1 adipocytes, as shown by Oil red O staining, compared to Control and SK (P < 0.05). SK and A-FK reduced adipo-/lipogenesis related genes such as $C/EBP{\alpha}$, SREBP-1, LPL, and $LXR{\alpha}$ compared to Control (P < 0.05). Especially, A-FK more greatly reduced SREBP-1 and LPL compared to SK (P < 0.05). A-FK up-regulated the ${\beta}$-oxidation related gene CPT-1c and down-regulated the pro-inflammatory cytokine IL-6 compared to Control (P < 0.05). Based on the results, A-FK exhibited anti-obesity effects by inhibiting fat droplet formation and adipo-/lipogenesis related genes by regulating the ${\beta}$-oxidation related gene CPT-1c and pro-inflammatory cytokine IL-6. In previous studies, A-FK kimchi already exhibited a strong anti-cancer effect. These results indicate that A-FK increased anti-obesity activity in this model system due to its functional ingredients and anti-cancer functionality.

• Nutrition Research and Practice
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• v.18 no.1
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• pp.19-32
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• 2024

BACKGROUND/OBJECTIVES: Atherosclerosis is associated with increased inflammation in the visceral adipose tissue (VAT). Vitamin D has been reported to modulate the inflammatory responses of stromal vascular cells (SVCs) and adipocytes in adipose tissue, but the role of vitamin D in atherosclerosis biology is unclear. This study examined the effects of in vitro 1,25-dihydroxyvitamin D₃ (1,25[OH]₂D₃) treatment on the inflammatory responses of SVCs and adipocytes from atherosclerotic mice. MATERIALS/METHODS: C57BL/6J (B6) mice were divided randomly into 2 groups and fed a 10% kcal fat control diet (control group, CON) or 41% kcal fat, 0.21% cholesterol (high fat + cholesterol, HFC) diet (obese group, OB), and B6.129S7-Ldlr^tm1Her/J (Ldlr^-/-) mice were fed a HFC diet (obese with atherosclerosis group, OBA) for 16 weeks. SVCs and adipocytes isolated from VAT were pre-incubated with 1,25(OH)₂D₃ for 24 h and stimulated with lipopolysaccarides for the next 24 h. Proinflammatory cytokine production by adipocytes and SVCs, the immune cell population in SVCs, and the expression of the genes involved in the inflammatory signaling pathway in SVCs were determined. RESULTS: The numbers of total macrophages and SVCs per mouse were higher in OB and OBA groups than the CON group. The in vitro 1,25(OH)₂D₃ treatment significantly reduced macrophages/SVCs (%) in the OBA group. Consistent with this change, the production of interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) by SVCs from the OBA group was decreased by 1,25(OH)₂D₃ treatment. The 1,25(OH)₂D₃ treatment significantly reduced the toll-like receptor 4 and dual-specificity protein phosphatase 1 (also known as mitogen-activated protein kinase phosphatase 1) mRNA levels in SVCs and MCP-1 production by adipocytes from all 3 groups. CONCLUSIONS: These findings suggest that vitamin D can attribute to the inhibition of the inflammatory response in VAT from atherosclerotic mice by reducing proinflammatory cytokine production.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.3
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• pp.357-364
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• 1999

We investigated the role of $Ca^{2+}$ and protein kinases/phosphatases in the stimulatory effect of insulin on glucose transport. In isolated rat adipocytes, the simple omission of $CaCl_2$ from the incubation medium significantly reduced, but did not abolish, insulin-stimulated 2-deoxy glucose (2-DG) uptake. Pre-loading adipocytes with intracellular $Ca^{2+}$ chelator, 5,5'-dimethyl bis (o-aminophenoxy)ethane-N,N,N'N' tetraacetic acetoxymethyl ester (5,5'-dimethyl BAPTA/AM) completely blocked the stimulation. Insulin raised intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ about 1.7 times the basal level of $72{\pm}5$ nM, and 5,5'-dimethyl BAPTA/AM kept it constant at the basal level. This correlation between insulin-induced increases in 2-DG uptake and $[Ca^{2+}]_i$ indicates that the elevation of $[Ca^{2+}]_i$ may be prerequisite for the stimulation of glucose transport. Studies with inhibitors (ML-9, KN-62, cyclosporin A) of $Ca^{2+}-calmodulin$ dependent protein kinases/phosphatases also indicate an involvement of intracellular $Ca^{2+}.$ Additional studies with okadaic acid and calyculin A, protein phosphatase-1 (PP-1) and 2A (PP-2A) inhibitors, indicate an involvement of PP-1 in insulin action on 2-DG uptake. These results indicate an involvement of $Ca^{2+}-dependent$ signaling pathway in insulin action on glucose transport.

• Natural Product Sciences
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• v.22 no.2
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• pp.122-128
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• 2016

This paper reports in vitro cytotoxic, anti-inflammatory and adipocyte diffentiation with adipogenic effects of coumarins inophyllum D (1) and calanone (2), and a chromanone carboxylic acid namely isocordato-oblongic acid (3) isolated from Calophyllum symingtonianum as well as a biflavonoid morelloflavone (4) isolated from Garcinia prainiana on MCF-7 breast adenocarcinoma RAW 264.7 macrophages and 3T3-L1 preadipocytes cells, respectively. The cytotoxicity study on MCF-7 cell was conducted by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Meanwhile, the study of anti-inflammatory effects in RAW 264.7 macrophages and adipogenic effects on 3T3-L1 pre-adipocytes were conducted through nitrite determination assay and induction of adipocyte differentiation, respectively. In the cytotoxicity study, inophyllum D (1) was the only compounds that exhibited significant cytotoxic effect against MCF-7 cell with $IC_{50}$ of $84{\mu}g/mL$. Further, all by inhibiting the compounds have shown anti-inflammatory effects in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages of nitrite concentration with production. In addition, the compounds also exhibited adipogenic effects on 3T3-L1 pre-adipocytes by stimulating lipid formation. Thus, this study may provide significant input in discovery of the potential effects cytotoxic, anti-inflammatory and adipogenic agents.

• Journal of Microbiology and Biotechnology
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• v.31 no.7
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• pp.1011-1021
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• 2021

The root bark of Ulmus davidiana var. japonica (Japanese elm) is used in Korea and other East Asian countries as a traditional herbal remedy to treat a variety of inflammatory diseases and ailments such as edema, gastric cancer and mastitis. For this study, we investigated the lipid metabolism and anti-obesity efficacy of ethyl alcohol extract of Ulmus davidiana var. japonica root bark (UDE). First, HPLC was performed to quantify the level of (+)-catechin, the active ingredient of UDE. In the following experiments, cultured 3T3-L1 pre-adipocytes and high-fat diet (HFD)-fed murine model were studied for anti-obesity efficacy by testing the lipid metabolism effects of UDE and (+)-catechin. In the test using 3T3-L1 pre-adipocytes, treatment with UDE inhibited adipocyte differentiation and significantly reduced the production of adipogenic genes and transcription factors PPARγ, C/EBPα and SREBP-1c. HFD-fed, obese mice were administered with UDE (200 mg/kg per day) and (+)-catechin (30 mg/kg per day) by oral gavage for 4 weeks. Weight gain, epididymal and abdominal adipose tissue mass were significantly reduced, and a change in adipocyte size was observed in the UDE and (+)-catechin treatment groups compared to the untreated control group (^***p < 0.001). Significantly lower total cholesterol and triglyceride levels were detected in UDE-treated HFD mice compared to the control, revealing the efficacy of UDE. In addition, it was found that lipid accumulation in hepatocytes was also significantly reduced after administration of UDE. These results suggest that UDE has significant anti-obesity and lipid metabolism effects through inhibition of adipocyte differentiation and adipogenesis.

• Journal of Life Science
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• v.26 no.3
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• pp.325-330
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• 2016

In this study, we evaluated the antidiabetic effect of submerged culture of Ceriporia lacerata mycelium (CL01) on glucose uptake and the expression of mRNA and protein of major signal markers of insulin signaling pathway in 3T3-L1 adipocytes. After 3T3-L1 adipocytes were pre-treated by CL01 (0, 2, 10 mg/ml) for 8 hours, followed with treatment of insulin, the glucose uptake levels significantly increased by more 55.1%, 94.4% than negative control respectively (p<0.01, 0.001) in a dose-dependent manner. However, in case of CL01 pre-treatment without insulin, the glucose uptake did not increase compared with insulin-treated 3T3-L1. Also we demonstrated that the protein expression levels of pIR β, pAkt, pPI3K and pAMPK and the mRNA expression levels of GLUT4 in adipocytes inducing insulin resistance increased in CL01-treated group compared with negative control. These results demonstrated that CL01 affected glucose metabolism and the protein and gene expression through insulin signaling pathway, and increased glucose uptake levels effectively. More than 90% of those who have suffered for type 2 diabetes are more likely to have from hyperinsulinemia, hypertension, obesity and etc. because of altered insulin signaling pathway. So, it is probably considered that intake of CL01 may treat type 2 diabetes by normalization of insulin signaling pathway, and it will provide useful evidences regarding a mechanism for cure of type 2 diabetes.

• Microbiology and Biotechnology Letters
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• v.44 no.1
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• pp.89-97
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• 2016

Obesity is caused by excess accumulation of body fat and contributes to various pathological disorders such as diabetes, hypertension, cardiovascular disease, and cancer. In this study, we investigated the effect of a 30% ethanol extract of Fructus Rosae laevigata (RLE) on adipogenesis in 3T3-L1 adipocytes, measured by triglyceride accumulation and expression of adipogenesis-related transcription factors during differentiation of pre-adipocytes into adipocytes. RLE decreased the intracellular triglyceride contents (assessed by Oil Red-O staining) in a dose-dependent manner. It also downregulated the expression of adipogenic transcription factors and inhibited cell proliferation during the mitotic clonal expansion phase of adipocyte differentiation by inducing G1 phase arrest. We investigated the alterations in the levels of G1 phase arrest-related proteins. The expression of p21 protein significantly increased, while the levels of Cyclin E, Cdk2, and phospho-Rb decreased in a dose-dependent manner in 3T3-L1 cells treated with RLE. These results suggest that RLE inhibits the differentiation of 3T3-L1 adipocytes by suppressing the expression of adipogenic transcription factors and inducing G1 phase arrest in the early stages of adipocyte differentiation.

• Nutrition Research and Practice
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• v.12 no.6
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• pp.494-502
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• 2018

BACKGROUND/OBJECTIVES: Reducing the number of adipocytes by inducing apoptosis of mature adipocytes as well as suppressing differentiation of preadipocytes plays an important role in preventing obesity. This study examines the anti-adipogenic and pro-apoptotic effect of red pepper seed water extract (RPS) prepared at $4^{\circ}C$ (RPS4) in 3T3-L1 cells. MATERIALS/METHODS: Effect of RPS4 or its fractions on lipid accumulation was determined in 3T3-L1 cells using oil red O (ORO) staining. The expressions of AMP-activated protein kinase (AMPK) and adipogenic associated proteins [peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR-{\gamma}$), CCAAT/enhancer-binding proteins ${\alpha}$ (C/EBP ${\alpha}$), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC)] were measured in 3T3-L1 cells treated with RPS4. Apoptosis and the expression of Akt and Bcl-2 family proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad), Bcl-2 like protein 4 (Bax), Bal-2 homologous antagonist/killer (Bak)] were measured in mature 3T3-L1 cells treated with RPS4. RESULTS: Treatment of RPS4 ($0-75{\mu}g/mL$) or its fractions ($0-50{\mu}g/mL$) for 24 h did not have an apparent cytotoxicity on pre and mature 3T3-L1 cells. RPS4 significantly suppressed differentiation and cellular lipid accumulation by increasing the phosphorylation of AMPK and reducing the expression of $PPAR-{\gamma}$, C/EBP ${\alpha}$, SREBP-1c, FAS, and ACC. In addition, all fractions except ethyl acetate fraction significantly suppressed cellular lipid accumulation. RPS4 induced the apoptosis of mature adipocytes by hypophosphorylating Akt, increasing the expression of the pro-apoptotic proteins, Bak, Bax, and Bad, and reducing the expression of the anti-apoptotic proteins, Bcl-2 and p-Bad. CONCLUSIONS: These finding suggest that RPS4 can reduce the numbers as well as the size of adipocytes and might useful for preventing and treating obesity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.6
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• pp.814-821
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• 2014

As a natural plant ingredients, glasswort (Salicornia herbacea L.) contains various physiological activities, mainly anti-oxidative and anti-diabetic activities. However, only a few studies have been carried out on its anti-adipogenic effect. This study investigated the anti-obesity effects of Salicornia herbacea L. on 3T3-L1 adipocytes. As adipogenesis of preadipocytes to adipocytes involves proliferation and differentiation of cells, we treated three concentrations (125, 250, and $500{\mu}g/mL$) of Salicornia herbacea L. water extracts (SLW) in both pre-processing and post-processing stages. When 3T3-L1 adipocytes were differentiated and dyed with Oil Red O, adipocytes size and the value of relative Oil Red O staining were reduced by all concentrations of SLW in post-processing stage. Following adipogenic differentiation, the concentration of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in the cell supernatant significantly increased upon treatment with $125{\mu}g/mL$ of SLW and further rose at concentrations of 250 and $500{\mu}g/mL$ during post-processing stage. There was no significant difference in glycerol production upon SLW treatment. Leptin production significantly decreased at all SLW concentrations during post-processing stage, whereas peroxisome proliferator activated receptor-${\gamma}$ (PPAR-${\gamma}$) and adiponectin secretions were significantly enhanced. Overall results showed that SLW might have an anti-adipogenic effect via enhancement of TNF-${\alpha}$ production, which causes dedifferentiation and inhibits lipid accumulations in adipocyte. Furthermore, SLW might prevent diabetes and cardiovascular disease, as it reduces leptin secretion and enhances production of both PPAR-${\gamma}$ and adiponectin. However, further research is needed to elucidate the exact mechanism and bioactive compounds of glasswort.