• The Korea Journal of Herbology
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• v.33 no.2
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• pp.69-77
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• 2018

Objectives : Daesiho-tang (DSHT) has been widely used in the treatment of cerebral infarct in traditional medicine. However, there was not report on the anti-obesity-related diseases efficacy of DSHT. In this study, we investigated the effects for the new formulation of DSHT, on the adipocyte differentiation cycle in 3T3-L1 cells. Methods : 3T3-L1 cells were treated with DSHT (50, 100, $200{\mu}g/m{\ell}$) during differentiation for 6 days. Also, the inhibitory effect of DSHT against 3T3-L1 adipogenesis was evaluated in various stage of adipogenesis such as early (0-2day), intermediate (2-4day), and terminal stage (4-6day). The accumulation of lipid droplets was determined by Oil Red O staining. and, the expressions of genes related to adipogenesis were measured by RT-PCR and Western blot analyses. Results : DSHT showed inhibitory activity on adipocyte differentiation at 3T3-L1 preadipocytes without affect cell toxicity as assessed by measuring fat accumulation and adipogenesis. In addition, DSHT significantly reduced the expression levels of several adipocyte marker genes including proliferator activated $receptor-{\gamma}$ ($PPAR-{\gamma}$) and CCAAT/ enhancer-binding $protein-{\alpha}$ ($C/EBP-{\alpha}$). Also, the anti-adipogenic effect of DSHT was strongly limited in the intermediate (2-4 day), terminal stage (4-6 day) of 3T3-L1 adipogenesis. In addition, the DSHT treatment down- regulated mRNA expression levels of $PPAR-{\gamma}$,, $C/EBP-{\alpha}$ in mature 3T3-L1 adipocytes. Conclusions : These results suggest that, the ability of DSHT has inhibited overall adipogenesis and lipid accumulation in the 3T3-L1 cells. The new formulation of DSHT may be a promising medicine for the treatment of obesity and related metabolic disorders.

• Journal of Life Science
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• v.33 no.3
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• pp.295-303
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• 2023

Immune and metabolic systems are important factors in maintaining homeostasis. Immune response and metabolic regulation are highly associated, so, when the normal metabolism is disturbed, the immune response changed followed the metabolic diseases occur. Likewise, obesity is highly related to immune response. Obesity, which is caused by an imbalance in energy metabolism, is associated with metabolic diseases, such as insulin resistance, type 2 diabetes, fatty liver diseases, atherosclerosis and hypertension. As known, obesity is characterized in chronic low-grade inflammation. In obesity, the microenvironment of immune cells became inflammatory by the unique activation phenotypes of immune cells such as macrophage, natural killer cell, T cell. Also, the immune cells interact each other in cellular or cytokine mechanisms, which intensify the obesity-induced inflammatory response. This phenomenon suggests the possibility of regulating the activation of immune cells as a pharmacological therapeutic strategy for obesity in addition to the common pharmacological treatment of obesity which is aimed at inhibiting enzymes such as pancreatic lipase and α-amylase or inhibiting differentiation of preadipocytes. In this review, we summarize the activation phenotypes of macrophage, natural killer cell and T cell, and their aspects in obesity. We also summarize the pharmacological substances that alleviates obesity by regulating the activation of immune cells.

• Animal Bioscience
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• v.37 no.5
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• pp.929-943
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• 2024

Objective: The present study was executed to explore the molecular mechanism of fibroblast growth factor 10 (FGF10) gene in bovine adipogenesis. Methods: The bovine FGF10 gene was overexpressed through Ad-FGF10 or inhibited through siFGF10 and their negative control (NC) in bovine adipocytes, and the multiplicity of infection, transfection efficiency, interference efficiency were evaluated through quantitative real-time polymerase chain reaction, western blotting and fluorescence microscopy. The lipid droplets, triglycerides (TG) content and the expression levels of adipogenic marker genes were measured during preadipocytes differentiation. The differentially expressed genes were explored through deep RNA sequencing. Results: The highest mRNA level was found in omasum, subcutaneous fat, and intramuscular fat. Moreover, the highest mRNA level was found in adipocytes at day 4 of differentiation. The results of red-oil o staining showed that overexpression (Ad-FGF10) of the FGF10 gene significantly (p<0.05) reduced the lipid droplets and TG content, and their down-regulation (siFGF10) increased the measurement of lipid droplets and TG in differentiated bovine adipocytes. Furthermore, the overexpression of the FGF10 gene down regulated the mRNA levels of adipogenic marker genes such as CCAAT enhancer binding protein alpha (C/EBPα), fatty acid binding protein (FABP4), peroxisome proliferator-activated receptor-γ (PPARγ), lipoprotein lipase (LPL), and Fas cell surface death receptor (FAS), similarly, down-regulation of the FGF10 gene enriched the mRNA levels of C/EBPα, PPARγ, FABP4, and LPL genes (p<0.01). Additionally, the protein levels of PPARγ and FABP4 were reduced (p<0.05) in adipocytes infected with Ad-FGF10 gene and enriched in adipocytes transfected with siFGF10. Moreover, a total of 1,774 differentially expressed genes (DEGs) including 157 up regulated and 1,617 down regulated genes were explored in adipocytes infected with Ad-FGF10 or Ad-NC through deep RNA-sequencing. The top Kyoto encyclopedia of genes and genomes pathways regulated through DEGs were the PPAR signaling pathway, cell cycle, base excision repair, DNA replication, apoptosis, and regulation of lipolysis in adipocytes. Conclusion: Therefore, we can conclude that the FGF10 gene is a negative regulator of bovine adipogenesis and could be used as a candidate gene in marker-assisted selection.

• Food Science and Preservation
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• v.30 no.3
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• pp.502-513
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• 2023

This study aimed to evaluate the anti-adipogenic and anti-inflammation effects of extract from Maclura tricuspidata twig fermented with Ganoderma lucidum mycelium (EMFG) in 3T3-L1 preadipocytes. 3T3-L1 adipocytes were treated with 100, 200, 300 ㎍/mL of EMFG. The result showed that EMFG dose-dependently inhibited the accumulation of intracellular lipid content in differentiated 3T3-L1 adipocytes and enhanced increase of adiponectin release and inhibition of leptin release. EMFG treatment reduced expression of adipogenic transcriptional factor such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα). EMFG also decreased production of lipopolysaccharide (LPS)-induced inflammatory cytokine [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1)] and the protein expression of cyclooxygenase-2 (COX-2) and inducible NOS (iNOS) in differentiated 3T3-L1 adipocytes. The study demonstrated that EMFG inhibited adipogenesis and inflammation in a dose-dependent manner. These findings suggest that EMFG may have potential as an anti-obesity and anti-metabolic disease agent that works by inhibiting adipogenesis and inflammation.

• Food Science and Preservation
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• v.30 no.4
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• pp.716-728
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• 2023

The anti-adipogenic activity of Glycyrrhiza uralensis was investigated by examining the effects of its ethanol extract (GUE) on a mouse model with a high-fat diet (HFD) and 3T3-L1 preadipocytes during adipocyte differentiation. GUE administration for eight weeks significantly reduced weight gain in mice fed an HFD. GUE effectively inhibited 3T3-L1 preadipocyte differentiation and lipid droplet accumulation. This inhibitory effect is associated with the downregulation of key adipogenic regulators, including PPARγ and C/EBPα, and the modulation of adipose metabolism regulators, such as Fasn and Fabp4. LC-Q-TOF-MS analysis identified twelve phenolic and flavonoid compounds, including liquiritigenin and licorice saponin, in the GUE. These findings demonstrate that the anti-obesity effect of the GUE is attributed to the biological activity of its phenolic and flavonoid compounds. Therefore, the GUE has potential anti-obesity activity. Moreover, further studies on the isolation of bioactive components from the GUE and the investigation of the underlying molecular mechanisms of the GUE are required to establish its efficacy in metabolic disorders, including obesity.

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

BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)₂D₃ after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)₂D₃ during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)₂D₃ treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)₂D₃ administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)₂D₃ inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)₂D₃ treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)₂D₃ prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.

• Journal of Applied Biological Chemistry
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• v.66
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• pp.369-378
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• 2023

Smilax sieboldii is one of the Smilax species. A number of Smilax plants have multiple physiologically-active components and anti-inflammatory/anti-oxidant effects. Antiobesity effects induced by Smilax sieboldii have not been reported. In this study, we investigated the effects and molecular mechanisms of anti-obesity activity of 70% ethanol Smilax sieboldii extract (SSE). The anti-obesity effect of SSE was determined using 3T3-L1 adipocytes. We confirmed that SSE was not cytotoxic to murine 3T3-L1 preadipocytes, we evaluated SSE dose-dependently decreased the accumulation of lipids via an Oil Red O assay and triglyceride assay. These anti-obesity activities of SSE were mediated by the inhibition of adipogenesis-related marker genes (peroxisome proliferator activated receptor-γ, CCAAT-enhancer-binding protein α, and SREBP1c) and lipogenesis-related marker genes (fatty acid synthase and aP2). These results suggest that SSE has the potential to exert anti-obesity and anti-hyperlipidemia effects by regulating adipogenic transcription factors and inhibiting the expression of adipogenic markers.

• Journal of Animal Science and Technology
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• v.47 no.6
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• pp.1087-1094
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• 2005

The uptake of glucose for metabolism and growth is essential to most animal cells and is mediated by glucose transport protein. In the glucose transport protein family, GLUT4 plays a key role in cellular glucose uptake stimulated by insulin in skeletal muscles and adipose tissue in rodents and human. In this studies, we reported the identification, characterization, and expression of Hanwoo GLUT4 gene. The Hanwoo GLUT4 cDNA includes a 1527 bp open reading frame encoding a protein of 509 amino acids. The GLUT4 amino acid sequences of the Hanwoo show strong conservation with the corresponding sequences reported in other species. The highest mRNA expression of GLUT4 was detected in heart and lower expression was detected in rib meat, sirloin, and colon. We confirmed the expression of GLUT4 in the subcutaneous and small intestinal adipose tissue using RT-PCR. To investigate the expression of GLUT4 in the bovine intramuscular adipose differentiation, fibroblast-like cells were isolated from the sirloin of Hanwoo bull aged 12 months by collagenase digestion of minced tissue and cultured with activators of PPAR gamma. We identified that GLUT4 mRNA expression decreased during differentiation of preadipocytes into adipocyte in Korean cattle. These results indicated that function of GLUT4 in bovine adipose tissue was different from that of mouse and human.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.3
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• pp.279-288
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• 2017

This study investigated the manufacturing of fermented soybean oil using a fermenting strain commonly processed for soybeans [Bacillus amyloliquefaciens (BA), Bacillus subtilis (BS), Lactobacillus acidophilus (LBA), and B. subtilis+L. acidophilus (BLO)] and evaluated its anti-obesity activities. Cytotoxicity of four kinds of fermented soybean oils was not observed in 3T3-L1 preadipocytes at 10 and $50{\mu}g/mL$. Triglyceride content was reduced by 20.6% in the BLO group at a treatment concentration of $50{\mu}g/mL$. The simultaneous treatment of fermented soybean oil and differentiation induction medium decreased $PPAR{\gamma}$ and $C/EBP{\alpha}$ gene expression at a concentration of $50{\mu}g/mL$ and blocked adipocyte differentiation by increasing adiponectin gene expression. The inhibitory effect of adipocyte differentiation was greatest in the BLO group. C57BL/6J mice were examined for 4 weeks after being separated into seven groups [normal diet group (N), high fat diet group (C), group fed high fat diet combined with regular soybean oil (SO), group fed non-fermented soybean oil (NF), and groups fed high fat diet combined with 5% fermented soybean oil (BA, BS, LBA, and BLO)] to identify the effects of soybean oil on body weight, serum lipid, adiponectin, insulin, and leptin levels in mice with high fat diet-induced obesity. The body weight and serum lipid level of the C group increased drastically compared to those of the N group. In contrast, the group fed a diet combined with fermented soybean oil showed decreases in weight, serum total cholesterol, LDL-cholesterol, and triglyceride levels compared to those of the C group. Moreover, soybean oil was found to be effective in the BLO group. In conclusion, fermented soybean oil has positive effects in prohibiting adipocyte differentiation increased by high fat diet and improving serum lipid composition. Therefore, fermented soybean oil can be used as a functional food material with anti-obesity activity.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.4
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• pp.624-629
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• 2014

Obesity is the leading metabolic disease in industrialized countries and is closely associated with coronary heart disease, hypertension, diabetes, and cancer. The objective of this study was to evaluate the anti-adipogenic effects of two roasted coffee beans, Vietnam robusta (VR) and Ethiopia Mocha Sidamo G2 (ES), as well as fermented coffee beans with Monascus ruber (MR) mycelium on differentiation of 3T3-L1 preadipocytes. Treatments with 1,000 ${\mu}g/mL$ of hot water extract from coffee beans significantly reduced intracellular lipid accumulation. In addition, VR more effectively inhibited transcription factors such as $PPAR{\gamma}$, $C/EBP{\alpha}$, FAS, and aP2 compared to ES. Further, ES fermented with MR showed more effective anti-adipogenic activity than non-fermented ES. These results suggest that VR and ES inhibit adipocyte differentiation which may contribute to their anti-adipogenic properties.