• Korean Journal of Pharmacognosy
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• v.41 no.1
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• pp.21-25
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• 2010

The MeOH extract of Rhus verniciflua heartwood inhibited lipid accumulation in 3T3-L1 adipocytes. Chromatographic methods including of silica gel, RP-18 and high-pressure liquid chromatography isolated sulfuretin and fisetin from the extract as active constituents. The isolated compounds, especially sulfuretin, strongly inhibited lipid accumulation in adipocytes. The treatment of sulfuretin and fisetin led to decreased expression of peroxisome proliferator-activated receptor-gamma ($PPAR{\gamma}$), as an important transcription factor in fat cell differentiation, which was equal to the decrease in the quercetin positive control. The presence of a hydroxyl group (C-5) in quercetin compared to fisetin, and the presence of C-2 double bonds in fisetin compared with fustin increased the inhibitory effect of lipid accumulation.

• Korean Journal of Pharmacognosy
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• v.42 no.2
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• pp.201-208
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• 2011

Obesity occur from the imbalance between energy intake and energy expenditure. Obesity is a complex chronic disease that is suggested to cause other metabolic disorders such as type 2 diabetes, hyperlipidemia, hypertension, and arteriosclerosis. In this study, our purpose is to investigate the anti-hyperglycemic and anti-obesitic effects of Maydis stigma water extract in 3T3-L1 adipocytes and db/db mice. Maydis stigma water extract at dose of 100 and 500 ${\mu}g/ml$ slowly inhibited cell viability as compared to that of control in mature adipocytes. Also, the additions of 50 and 250 ${\mu}g/ml$ of Maydis stigma water extract significantly inhibited the lipid accumulations and CCAAT/enhancer-binding protein(C/EBP) ${\alpha}$ and peroxisome proliferator-activated receptor(PPAR) ${\gamma}$ expressions with dose-dependent manner in 3T3-L1 adipocytes. Maydis stigma water extract at 250, 500, and 1000 ${\mu}g/ml$ only showed the increasing pattern on lipolysis activity. The oral treatment of Maydis stigma water extract (100 or 400 mg/kg body weight) in db/db mice only showed tendency to decrease body weight, food efficiency ratio (FER), HbA1c, blood glucose, total cholesterol, triglyceride, and the adipocyte size of in db/db mice. However, Maydis stigma water extract increased the insulin level in a dose dependent manner. Thus these results indicate that Maydis stigma water extracxt inhibits adipogenesis through regulation of C/EBP${\alpha}$ and PPAR${\gamma}$ expressions in 3T3-L1 adipocytes and shows anti-hyperglycemic effect through increase of insulin secretion in db/db mice.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.158-164
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• 2014

BACKGROUD/OBEJECTIVES: This study aims to find out the effects of peanut sprout extracts on weight controls and protein expressions of transcription factors related to adipocyte differentiation and adipocytokine in rats under high-fat diets. MATERIALS/METHODS: Four week-old Sparague-Dawley (SD) were assigned to 4 groups; normal-fat (NF) diets (7% fat diet), high-fat (HF) diets (20% fat diet), high fat diets with low peanut sprout extract (HF + PSEL) diet (20% fat and 0.025% peanut sprout extract), and high fat diets with high peanut sprout extract (HF + PSEH) diet (20% fat and 0.05% peanut sprout extract). Body weight changes, lipid profiles in adipose tissue, and the mRNA protein expressions, such as peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), CCAAT element binding protein ${\alpha}$ (C/EBP ${\alpha}$), leptin, and adiponectin, were determined. RESULTS: After 9 weeks of feeding, the HF + PSEH group had significantly less weight gains than the HF group (P < 0.05). However, the total dietary intakes or food efficiency ratios among groups were not significantly different. The weight of epididymal fat in HF + PSEH group, $3.61{\pm}0.5g$, or HF + PSEL group, $3.80{\pm}0.7g$, was significantly lower than the HF group, $4.39{\pm}0.4g$, (P < 0.05). Total lipids and total cholesterol in adipose tissue were significantly decreased in HF + PSEH group compared to those in the HF group, respectively (P < 0.05). PSEH supplementation caused AST and ALT levels to decrease when it compared to HF group, but it was not statistically significant. The protein expression of $PPAR{\gamma}$ in HF + PSEH group was significantly lower than the HF group (P < 0.05). Comparing with the HF group, the protein expression of adiponectin in HF + PSEH group was significantly increased (P < 0.05). The protein expressions of C/EBP ${\alpha}$ and leptin in HF + PSEH group were lower than the HF group, but it was not statistical significant. CONCLUSIONS: In conclusion, peanut sprout extract has anti-obesity effect by lowering the expressions of $PPAR{\gamma}$ which regulates the expression of adiponectin.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.15-21
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• 2014

Objectives : The purpose of this study was to investigate inhibitory effects of steamed Polygonatum odoratum extract (POE) on differentiation and adipogenesis in 3T3-L1 adipocytes. Methods : Polygonatum odoratum (P. odoratum) extract was extracted with ethyl acetate. Total phenolic and flavonoid contents in POE were measured for antioxidant activity. The spectrophotometric method was used to determine the DPPH and ABTS radical scavenging activity and ferric-reducing antioxidant potential (FRAP). MTT assay was examined for cell toxicity, oil red O staining was performed for intracelluar adipogenesis in differentiated 3T3-L1 adipocytes. Western blot analysis for measurement of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor${\gamma}$ ($PPAR{\gamma}$) and AMP-activated protein kinase (AMPK) expressions were performed. Results : The results revealed that POE has antioxidant activities. Contents of total polyphenolics and flavonoids were $50.83{\pm}1.52$ GAE mg/100g dry weight of POE and $17.05{\pm}2.47$ RE mg/100g dry weight of POE, respectively. DPPH radical scavenging activity, and FRAP in 10 mg/ml concentration were $92.1{\pm}0.6%$, $244.8{\pm}9.0{\mu}M$ Fe(II) and ABTS inhibition in 5 mg/ml concentration was $84.8{\pm}4.1%$. Treatment of POE in adipocytes inhibited the differentiation and adipogenesis of 3T3-L1 adipocytes compared to those of vehicle control. Additionally, protein expressions of $C/EBP{\alpha}$ and $PPAR{\gamma}$, major transcription factor for the adipogenic genes, were significantly decreased compared to those of vehicle control (p<0.05). Futhermore, phosphorylation of AMPK was increased in 3T3-L1 adipocytes treated with POE compared to that of vehicle control (p<0.05). Conclusions : we demonstrate that steamed P. odoratum extract (POE) has potentiating antioxidant activities, inhibits differentiation and lipid accumulation and also induces energy expenditure in adipocytes, which may contribute to antiobesity property.

• Journal of Yeungnam Medical Science
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• v.36 no.1
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• pp.26-35
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• 2019

Background: Dysregulation of hepatic glucose production (HGP) contributes to the development of type 2 diabetes mellitus. Telmisartan, an angiotensin II type 1 receptor blocker (ARB), has various ancillary effects in addition to common blood pressure-lowering effects. The effects and mechanism of telmisartan on HGP have not been fully elucidated and, therefore, we investigated these phenomena in hyperglycemic HepG2 cells and high-fat diet (HFD)-fed mice. Methods: Glucose production and glucose uptake were measured in HepG2 cells. Expression levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase ${\alpha}$ ($G6Pase-{\alpha}$), and phosphorylation levels of insulin receptor substrate-1 (IRS-1) and protein kinase C ${\zeta}$ ($PKC{\zeta}$) were assessed by western blot analysis. Animal studies were performed using HFD-fed mice. Results: Telmisartan dose-dependently increased HGP, and PEPCK expression was minimally increased at a $40{\mu}M$ concentration without a change in $G6Pase-{\alpha}$ expression. In contrast, telmisartan increased phosphorylation of IRS-1 at Ser302 ($p-IRS-1-Ser^{302}$) and decreased $p-IRS-1-Tyr^{632}$ dose-dependently. Telmisartan dose-dependently increased $p-PKC{\zeta}-Thr^{410}$ which is known to reduce insulin action by inducing IRS-1 serine phosphorylation. Ectopic expression of dominant-negative $PKC{\zeta}$ significantly attenuated telmisartan-induced HGP and $p-IRS-1-Ser^{302}$ and -inhibited $p-IRS-1-Tyr^{632}$. Among ARBs, including losartan and fimasartan, only telmisartan changed IRS-1 phosphorylation and pretreatment with GW9662, a specific and irreversible peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$) antagonist, did not alter this effect. Finally, in the livers from HFD-fed mice, telmisartan increased $p-IRS-1-Ser^{302}$ and decreased $p-IRS-1-Tyr^{632}$, which was accompanied by an increase in $p-PKC{\zeta}-Thr^{410}$. Conclusion: These results suggest that telmisartan increases HGP by inducing $p-PKC{\zeta}-Thr^{410}$ that increases $p-IRS-1-Ser^{302}$ and decreases $p-IRS-1-Tyr^{632}$ in a $PPAR{\gamma}$-independent manner

• Journal of Microbiology and Biotechnology
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• v.18 no.6
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• pp.1170-1178
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• 2008

The cyclopentenone prostaglandins (cyPGs) prostaglandin $A_1$ ($PGA_1$) and 15-deoxy-${\Delta}^{12,14}$-prostaglandin $J_2$ (15d-$PGJ_2$) have been reported to exhibit antiinflammatory activity in activated monocytes/macrophages. However, the effects of these two cyPGs on the expression of cytokine genes may differ. In this study, we investigated the mechanism of action of $PGA_1$ in lipopolysaccharide (LPS)-induced expression of inter leu kin (IL)-10 mRNA in mouse peritoneal macrophages. 15d-$PGJ_2$ inhibited expression of LPS-induced IL-10, whereas $PGA_1$ increased LPS-induced IL-10 expression. This synergistic effect of $PGA_1$ on LPS-induced IL-10 expression reached a maximum as early as 2 h after simultaneous $PGA_1$ and LPS treatment ($PGA_1$/LPS), and did not require new protein synthesis. The synergistic effect of $PGA_1$ was inhibited by GW9662, a specific peroxisome proliferator-activated receptor ${\gamma}(PPAR{\gamma})$ antagonist, and Bay-11-7082, a NF-${\kappa}B$ inhibitor. The extracellular signal-regulated kinases (ERK) inhibitor PD98059 increased the expression of $PGA_1$/LPS-induced IL-10 mRNA, rather than inhibiting the IL-10 expression. Moreover, $PGA_1$ inhibited LPS-induced ERK phosphorylation. The synergistic effect of $PGA_1$ on LPS-induced IL-10 mRNA and protein production was inhibited by p38 inhibitor PD169316, and $PGA_1$ increased LPS-induced p38 phosphorylation. In the case of stress-activated protein kinase/c-Jun $NH_2$-terminal kinase (SAPK/JNK), the SAPK/JNK inhibitor SP600125 did not inhibit IL-10 mRNA synthesis but inhibited the production of IL-10 protein remarkably. These results suggest that the synergistic effect of $PGA_1$ on LPS-induced IL-10 expression is NF-${\kappa}B$-dependent and mediated by mitogen-activated protein (MAP) kinases, p38, and SAPK/JNK signaling pathways, and also associated with the $PPAR{\gamma}$ pathway. Our data may provide more insight into the diverse mechanisms of $PGA_1$ effects on the expression of cytokine genes.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1316-1321
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• 2012

Adipokines, adipocyte-derived protein, have important roles in various kinds of physiology including energy homeostasis. Chemerin, one of adipocyte-derived adipokines, is highly expressed in differentiated adipocytes and is known to induce macrophage chemotaxis and glucose intolerance. The objective of the present study was to investigate the changes of chemerin and the chemokine-like-receptor 1 (CMKLR1) gene expression levels during differentiation of the bovine adipocyte and in differentiated adipocytes treated with tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), adiponectin, leptin, and chemerin (peptide analog). The expression levels of the chemerin gene increased at d 6 and 12 of the differentiation period accompanied by increased cytoplasm lipid droplets. From d 6 onward, peroxisome proliferator-activated receptor-${\gamma}2$ (PPAR-${\gamma}2$) gene expression levels were significantly higher than that of d 0 and 3. In contrast, CMKLR1 expression levels decreased at the end of the differentiation period. In fully differentiated adipocytes (i.e. at d 12), the treatment of TNF-${\alpha}$ and adiponectin upregulated both chemerin and CMKLR1 gene expression levels, although leptin did not show such effects. Moreover, chemerin analog treatment was shown to upregulate chemerin gene expression levels regardless of doses. These results suggest that the expression of chemerin in bovine adipocyte might be regulated by chemerin itself and other adipokines, which indicates its possible role in modulating the adipokine secretions in adipose tissues.

• Korean Journal of Food Science and Technology
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• v.50 no.6
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• pp.688-696
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• 2018

This study aimed to investigate the effects of red ginseng-derived saponin fraction (SF) on lipid accumulation, reactive oxygen species (ROS) production, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) signaling during adipocyte differentiation. SF effectively inhibited lipid accumulation, with the downregulation of adipogenic factors such as peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) and CCAAT/enhancer-binding protein alpha ($C/EBP{\alpha}$). A high dose of SF decreased the protein levels of $PPAR{\gamma}$ and $C/EBP{\alpha}$ by over 90% compared to the control. SF-mediated downregulation of adipogenic factors was due to the regulation of early adipogenic factors including $C/EBP{\beta}$ and $Kr{\ddot{u}}ppel$-like Factor 2 (KLF2). In addition, SF ($200{\mu}g/mg$) decreased intracellular ROS generation by 40% during adipocyte differentiation. However, the SF significantly upregulated Nrf2 and its target proteins, hemoxygenase-1 (HO-1) and NADPH dehydrogenase quinone 1 (NQO1). Furthermore, SF ($200{\mu}g/mg$) promoted the nuclear translocation of Nrf2. The SF-mediated reduction of lipid accumulation was associated with the regulation of the Nrf2/Keap1 pathway.

• Asian-Australasian Journal of Animal Sciences
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• v.16 no.8
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• pp.1199-1204
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• 2003

The aim of this study was to investigate the role of phosphatidylinositol 3-kinase (PI3 kinase) and the mitogenactivating protein (MAP) kinase pathway on the differentiation of ovine preadipocytes. In order to investigate this issue, we monitored glycerol 3-phosphate dehydrogenase (GPDH) activity during differentiation with specific inhibitors of PI3 kinase and MAP kinase-Erk kinase, LY294002 and PD098059, respectively. The preadipocytes, which were obtained from ovine subcutaneous adipose tissues, were proliferated to confluence and then differentiated to adipocytes in differentiation medium with each inhibitor for 10 days. The confluent preadipocytes and differentiated adipocytes at days 3, 7 and 10 were harvested for assay of GPDH activity. LY294002 inhibited the differentiation program in dose- and day-dependent manners during 10 days of differentiation. PD098059 did not affect GPDH activity during differentiation. Furthermore, the expression of peroxisome proliferator-activated receptor ${\gamma}2$ (PPAR-${\gamma}2$), the representative early gene of differentiation, was markedly reduced by LY294002 treatment, although PD098059 did not change it. Our results demonstrated that the activation of PI3 kinase contributes to the differentiation process of ovine preadipocytes.

• Journal of Microbiology and Biotechnology
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• v.34 no.5
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• pp.1073-1081
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• 2024

Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease, arteriosclerosis, hypertension, and cancer, which are correlated with obesity, influence society and the economy. Suppression of adipogenesis, the process of white adipocyte generation, remains a promising approach for treating obesity. Oil Red O staining was used to differentiate 3T3-L1 cells for screening 20 distinct Lactobacillus species. Among these, Lactobacillus acidophilus DS0079, referred to as YBS1, was selected for further study. YBS1 therapy decreased 3T3-L1 cell development. Triglyceride accumulation and mRNA expression of the primary adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ), including its downstream target genes, adipocyte fatty acid binding protein 4 and adiponectin, were almost eliminated. YBS1 inhibited adipocyte differentiation at the early stage (days 0-2), but no significant difference was noted between the mid-stage (days 2-4) and late-stage (days 4-6) development. YBS1 stimulated the activation of p38 mitogen-activated protein kinase (p38 MAPK) during the early stages of adipogenesis; however, this effect was eliminated by the SB203580 inhibitor. The data showed that YBS1 administration inhibited the initial development of adipocytes via stimulation of the p38 MAPK signaling pathway, which in turn controlled PPARγ expression. In summary, YBS1 has potential efficacy as an anti-obesity supplement and requires further exploration.