• The Korean Journal of Food And Nutrition
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• v.30 no.5
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• pp.1035-1041
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• 2017

(-)-Epigallocatechin-3-gallate (EGCG) is a major catechin found in green tea. It is reported that EGCG possesses various health benefits including anti-cancer, antioxidant, anti-diabetes, and anti-obesity. The objective of this study was to investigate the effects of EGCG on adipogenesis via activation of AMP-activated protein kinase (AMPK) pathway in 3T3-L1 preadipocytes. In order to determine the effects of EGCG on adipogenesis, preadipocyte differentiation was induced in the presence or absence of EGCG ($0{\sim}100{\mu}M$) for a period of 6 days. EGCG significantly inhibited fat accumulation and suppressed the expression of adipogenic specific proteins including peroxisome proliferator-activated receptor (PPAR)-${\gamma}$. Also, EGCG markedly increased the activation of AMPK and acetyl-CoA carboxylase (ACC) and the production of intracellular reactive oxygen species (ROS). However, any pretreatment with a specific AMPK inhibitor, compound C, abolished the inhibitory effects of the EGCG on $PPAR{\gamma}$ expression. This study suggests that EGCG has anti-adipogenic effects through modulation of the AMPK signaling pathway and therefore, may be a promising antiobesity agent.

• Development and Reproduction
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• v.22 no.4
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• pp.351-360
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• 2018

The adipogenesis is a maturation process of pre-adipocyte cell into mature lipid-filled adipocyte cell. The adipogenesis begins at the late prenatal stage and continues until the early postnatal age. Because the adipogenesis and formation of adipose tissue persist during postnatal period and are precisely regulated by the action of numerous gene products, the present research was attempted to determine the expressional patterns of adipose tissue-associated genes in the rat epididymal fat pad at different postnatal ages, from 7 days to 2 years of ages, using a quantitative real-time PCR analysis. The basal expression levels of CCAAT/enhancer binding protein gamma, sterol regulatory element binding transcription factor 1, fatty acid binding protein 4, adiponectin, leptin, and resistin at the early postnatal ages were significantly lower than those at the elderly ages, even though a fluctuation of expressional levels was observed at some ages. The lowest expressional level of delta like non-canonical Notch ligand 1 was detected at 44 days and 5 months of ages. The expression of peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was the highest at 44 days of age, followed by a diminished expression of $PPAR{\gamma}$ at the elderly ages. These results indicate the existence of a complex regulatory mechanism(s) for expression of adipose tissueassociated genes in the rat epididymal fat during postnatal period.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.269-275
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• 2021

The in vitro anti-obesity activity of 12 species of tree sprouts in differentiated 3T3-L1 cells and the mechanisms underlying their activity were evaluated. (+)-Catechin and quercetin concentrations in the sprouts were analyzed by HPLC/UV at 270 and 254 nm, respectively. Euonymus alatus (EAT) and Fraxinus mandschuria (FMS) extracts at doses of 50 and 100 ㎍/mL inhibited the accumulation of lipid droplets in differentiated 3T3-L1 cells. Moreover, EAT and FMS downregulated the expression of the CCAAT/enhancer-binding protein-α, adipogenesis-related proteins peroxisome proliferator-activated receptor-γ, and adipocyte P-2α in differentiated 3T3-L1 cells. Tree sprouts with an abundant flavonoid content exerted the highest anti-obesity activity. Concentrations of total flavonoids were the highest in FMS (24.281 mg/g DW) sprouts. These findings could be used to develop health-promoting functional foods or supplements derived from tree sprouts.

• Journal of Veterinary Science
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• v.22 no.4
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• pp.53.1-53.13
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• 2021

Background: Canine adipose-derived stem cells (cADSCs) exhibit various differentiation properties and are isolated from the canine subcutaneous fat. Although cADSCs are valuable as tools for research on adipogenic differentiation, studies focusing on adipogenic differentiation methods and the underlying mechanisms are still lacking. Objectives: In this study, we aimed to establish an optimal method for adipogenic differentiation conditions of cADSCs and evaluate the role of peroxisome proliferator-activated receptor gamma (PPARγ) and estrogen receptor (ER) signaling in the adipogenic differentiation. Methods: To induce adipogenic differentiation of cADSCs, 3 different adipogenic medium conditions, MDI, DRI, and MDRI, using 3-isobutyl-1-methylxanthine (M), dexamethasone (D), insulin (I), and rosiglitazone (R) were tested. Results: MDRI, addition of PPARγ agonist rosiglitazone to MDI, was the most significantly facilitated cADSC into adipocyte. GW9662, an antagonist of PPARγ, significantly reduced adipogenic differentiation induced by rosiglitazone. Adipogenic differentiation was also stimulated when 17β-estradiol was added to MDI and DRI, and this stimulation was inhibited by the ER antagonist ICI182,780. Conclusions: Taken together, our results suggest that PPARγ and ER signaling are related to the adipogenic differentiation of cADSCs. This study could provide basic information for future research on obesity or anti-obesity mechanisms in dogs.

• Korean Circulation Journal
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• v.48 no.12
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• pp.1097-1119
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• 2018

Although elevated serum low-density lipoprotein-cholesterol (LDL-C) is without any doubts accepted as an important risk factor for cardiovascular disease (CVD), the role of elevated triglycerides (TGs)-rich lipoproteins as an independent risk factor has until recently been quite controversial. Recent data strongly suggest that elevated TG-rich lipoproteins are an independent risk factor for CVD and that therapeutic targeting of them could possibly provide further benefit in reducing CVD morbidity, events and mortality, apart from LDL-C lowering. Today elevated TGs are treated with lifestyle interventions, and with fibrates which could be combined with omega-3 fatty acids. There are also some new drugs. Volanesorsen, is an antisense oligonucleotid that inhibits the production of the Apo C-III which is crucial in regulating TGs metabolism because it inhibits lipoprotein lipase (LPL) and hepatic lipase activity but also hepatic uptake of TGs-rich particles. Evinacumab is a monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3) and it seems that it can substantially lower elevated TGs levels because ANGPTL3 also regulates TGs metabolism. Pemafibrate is a selective peroxisome proliferator-activated receptor alpha modulator which also decreases TGs, and improves other lipid parameters. It seems that it also has some other possible antiatherogenic effects. Alipogene tiparvovec is a nonreplicating adeno-associated viral vector that delivers copies of the LPL gene to muscle tissue which accelerates the clearance of TG-rich lipoproteins thus decreasing extremely high TGs levels. Pradigastat is a novel diacylglycerol acyltransferase 1 inhibitor which substantially reduces extremely high TGs levels and appears to be promising in treatment of the rare familial chylomicronemia syndrome.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.380.2-380.2
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• 2002

Peroxisome proliferator-activated receptor (PPAR)-$\gamma$ is a nuclear hormone receptor family that plays an important role in the transcriptional regulation of genes in cellular lipid and energy metabolism. In our search for Iigands for PPAR-$\gamma$ from natural resources. two phenylpropanoids. 3.4.5-Trimethoxy cinnamylalcohol (1) and 3.4.5- Trimethoxy cinnamaldehyde (2). were isolated as PPAR-$\gamma$ agonists from the MeOH extracts of Zanthoxylum schinifolium Sieb. & ZUCCo (Rutaceae) by activity-guided fractionation. These two compoundS bind and activated PPAR-$\gamma$ transcriptional activity in a dose dependent manner assessed by ligand-binding assay. While the maximum activities for PPAR-$\gamma$ of these compounds were comparable with that of rosiglitazone. which is currently used in the treatment of Type II diabetes. the potency of these compounds were much weaker than rosiglitazone ($ED_{50}$=t.2$\mu\textrm{M}$) with the $ED_{50}$ values of 9.08 and 4.08 $\mu\textrm{M}$. respectively. To examine the structure-activity relationship of phenylpropanoids. we prepared several phenylpropanoid derivatives and measured the activity. We observed that substituents at 4'- position could playa key role in determining the potency for PPAR-$\gamma$ agonistic activity .

• Biomedical Science Letters
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• v.27 no.1
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• pp.12-18
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• 2021

Hypertension (HTN) is one of the cardiovascular disease risk factors. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is involved in a master modulator of mitochondrial biogenesis, and pulmonary arterial hypertension. In this study, we report results of PPARGC1A were associated with hypertension and its intermediate phenotype of systolic (SBP) and diastolic blood pressure (DBP) in the Korean population. In detail, identifying a susceptibility locus, 3 SNPs for HTN, 2 SNPs for SBP, 3 SNPs for DBP at P<0.05. Among them, rs1472095 in PPARGC1A gene statistically demonstrated one of the significant correlations with Hypertension (P-value=0.00359, OR=0.8, 95% CI=0.68~0.93). The minor allele (T) of PPARGC1A was statistically associated with the increased value of DBP, SBP, and the increase risk of hypertension. We aim to manifest a significant association between genetic variant in PPARGC1A and hypertension. This finding suggested that association of PPARGC1A genetic polymorphism and HTN accelerates our understanding of blood pressure control and underlines potential drug targets for treatment of hypertension.

• Food Science of Animal Resources
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• v.41 no.1
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• pp.145-152
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• 2021

Microbial bioconversion using lactic acid bacteria (LAB) provides several human health benefits. Although whey and whey-derived bioactive compounds can contribute to an improvement in human health, the potential anti-obesity effect of whey bioconversion by LAB has not been well studied. This study aimed to investigate whether bioconversion of whey by Pediococcus pentosaceus KI31 and Lactobacillus sakei KI36 (KI31-W and KI36-W, respectively) inhibits 3T3-L1 preadipocyte differentiation. Both KI31-W and KI36-W reduced intracellular lipid accumulation significantly, without decreasing 3T3-L1 preadipocyte proliferation. In addition, obesity-related transcription factor (peroxisome proliferator-activated receptor γ) and genes (adipocyte fatty acid-binding protein and lipoprotein lipase) were down-regulated significantly in 3T3-L1 cells in the presence of KI31-W and KI36-W. Collectively, these results suggest that bioconversion of whey by LAB exhibits anti-adipogenic activity and may be applied as a therapeutic agent for obesity.

• Natural Product Sciences
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• v.28 no.2
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• pp.80-88
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• 2022

Colorectal cancer is one of the most common cancers globally, ranking second for the number of cancer-related deaths. Metastasis has been reported as the main cause of death in patients with colorectal cancer. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a transcription factor that functions as a tumor suppressor by inhibiting cellular proliferation, migration, and invasion. In our previous efforts to generate natural product-motivated PPAR-γ ligands, the compounds 1 and 2 were obtained. These compounds activated PPAR-γ and inhibited the migration and invasion of HCT116 colorectal cancer cells, and they were also found to inhibit the epithelial-to-mesenchymal transition, which is a key process in cancer metastasis. Compounds 1 and 2 upregulated expression of the epithelial marker (E-cadherin), and downregulated expression of the mesenchymal marker (N-cadherin) and transcriptional factor (Snail). Therefore, the PPAR-γ agonists 1 and 2 could serve as a valuable model for the study on anti-metastatic leads for the treatment of colorectal cancer.

• Natural Product Sciences
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• v.28 no.4
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• pp.161-167
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• 2022

Obesity is a complex metabolic disorder that increases the risk for type 2 diabetes, hyperlipidemia, hypertension, and atherosclerosis. In this study, we evaluated the anti-obesity effects of Nelumbo nucifera leaf (NL) extract in 3T3-L1 adipocytes and obese db/db mice. NL extract among various parts (leaf, seed, and root) of N. nucifera most effectively reduced adipogenesis via inhibiting CCAAT enhancer binding protein α (C/EBPα) and peroxisome proliferator activated receptor γ (PPARγ) expression in 3T3-L1 adipocytes. The addition of NL extract enhanced the protein expression of uncoupling protein 2 (UCP2) as compared to untreated 3T3-L1 adipocytes. The oral administration of NL extract (100 mg/kg BW) significantly reduced food efficacy ratio, body weight, and face or total cholesterol level in obese db /db mice. Also, administration of NL extract significantly decreased adipocyte size and C/EBPα or PPARγ expression in the adipose tissues as compared with control (obese db/db mice). Therefore, our results suggest that NL extract among various parts of N. nucifera could be used as a functional food ingredient for the prevention and treatment of metabolic diseases including obesity and diabetes.