• Journal of Life Science
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• v.21 no.5
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• pp.720-728
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• 2011

Garlic (Allium sativum) has been used as a source food as well as a traditional folk medicine ingredient since ancient times. Aged black garlic is a type of fermented garlic and is expected to have stronger anticancer and antioxidant activities than raw garlic. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis are poorly understood. In the present study, the effects and mechanisms of water extracts of raw garlic (WERG) and aged black garlic (WEABG) on adipocyte differentiation and adipogenesis in 3T3-L1 preadipocytes were investigated. Treatment with WEABG significantly suppressed terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner as confirmed by a decrease in lipid droplet number and lipid content through Oil Red O staining, however WERG had no such effect. In addition, WEABG reduced accumulation of cellular triglyceride, which is associated with a significant inhibition of key pro-adipogenic transcription factors including peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT)/enhancer binding proteins ${\alpha}$ (C/EBP${\alpha}$) and C/EBP${\beta}$. Taken together, these results provide important new insight that aged black garlic might inhibit adipogenesis by suppressing the pro-adipogenic transcription factors in 3T3-L1 preadipocytes, and further studies will be needed to identify the active compounds that confer the anti-obesity activity of aged black garlic.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.9
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• pp.1336-1343
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• 2005

In the present study, we screened candidates for enhancing insulin action and secretion from Cinnamomum camphora (CC) fractions, in 3T3-L1 adipocytes and Min6 cells by investigating insulin- stimulated glucose uptake and glucose-stimulated insulin secretion, respectively. CC were extracted by $70\%$ ethanol followed by XAD-4 column chromatography with serial mixture solvents of methanol and water, and the fractional extractions were utilized for determining insulin action and secretion, and $\alpha$-glucoamylase suppressing activity, A significant insulin-stimulated glucose uptake was observed in 3T3-L1 adipocytes, giving 0.5 or $5{\mu}g/mL$ of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin, compared to the treatment of DMSO plus 0.2 nM insulin. The treatments of $40\%\;and\;60\%$ methanol fractions plus 0.2 nM insulin reached the glucose uptake of 10 nM insulin treatment. The $40\%$ methanol fraction increased triglyceride accumulation by stimulating differentiation and triglyceride synthesis similar to pioglitazone, PPAR-$\gamma$ agonist. No inhibition of $\alpha$-glucoamylase activity of CC fractions was observed. They did not modulate the insulin secretion capacity In either low or high glucose media. These results suggest that $40\%$ methanol fraction contains a potential insulin sensitizer to have a similar function of PPAR-$\gamma$ agonist. Crude CC extract may improve glucose utilization by enhancing insulin-stimulated glucose uptake without elevating glucose stimulated insulin secretion.

• Journal of Korean Medicine for Obesity Research
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• v.4 no.1
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• pp.139-160
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• 2004

The obesity is detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms(SNPs), some of which promote the development of obesity-related type 2 diabetes mellitus. Type 2 diabetes mellitus is a common multifactorial genetic syndrome, which is determined by several different genes and environmental factors. In this review, five major conclusions are reached: (1)To be clinically significant, SNPs must be relevant, prevalent, modifiable, and measurable. (2)Differences in SNPs may have been caused by famine, ultraviolet light, alcohol, climate, agricultural revolution. livestock, lactase persistence, and westernized lifestyle. (3)Candidate obesity genes of calorie intake restriction are SIM 1, MC3R, MC4R, AGRP, CART, CCK, CNTFR, DRD2, Ghrelin, 5-HT receptor, NPY, PON and those of energy metabolism are LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, PGC-1, Androgen receptor and those of fat mobilization are AGT, ACE, ADA, APM1, Apolipoproteins, PPAR, FABP, FOXC2, GCGR, $11-{\beta}HSDI$, LDLR, Hormonal sensitive lipase, Perilipin, $TNF-{\alpha}$, $TNF-{\beta}$ (4)Candidate obesity genes in the eastern are NPY, LEP, LEPR, UCP1, UCP2, UCP3, B2AR, B3AR, ACE, APM1, PPAR, and FABP. (5)Candidate obesity genes in type 2 diabetes mellitus are MC3R, MC4R, B2AR, B3AR, ADA, APM1, PPAR, FABP, FOXC2, PC1, PC2, ABCC8, CAPN10, CYP19, CYP7, ENPP1, GCK, GYS1, IGF, IL-6, Insulin receptor, IRS, and LPL. The discovery of SNPs will lead to a greater understanding of the pathogenesis of obesity and to better diagnostics, treatment, and eventually prevention.

• Journal of Korean Medicine for Obesity Research
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• v.20 no.1
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• pp.1-9
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• 2020

Objectives: Artemisinin and its derivatives extracted from Artemisia annua, a Chinese herbal medicine, have variable biological effects due to structural differences. Up to date, the anti-obesity effect of dihydroartemisinin (DHA), a derivative of artemisinin, is unknown. The purpose of this study was to investigate the anti-adipogenic and lipolytic effects of DHA on 3T3-L1 preadipocytes. Methods: Oil Red O staining and AdipoRed assay were used to measure lipid accumulation and triglyceride (TG) content in 3T3-L1 cells, respectively. Cell count analysis was used to determine the cytotoxicity of 3T3-L1 cells. Western blot and real-time reverse transcription polymerase chain reaction analyses were used to analyze the expression of protein and mRNA in 3T3-L1 cells, respectively. Results: DHA at 5 μM markedly inhibited lipid accumulation and reduced TG content in differentiating 3T3-L1 cells with no cytotoxicity. Furthermore, DHA at 5 μM inhibited the expression of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A as well as the phosphorylation of signal transducer and activator of transcription-3 (STAT-3) in differentiating 3T3-L1 cells. Moreover, while DHA at 5 μM had no effect on the mRNA expression of adiponectin, it strongly suppressed that of leptin in differentiating 3T3-L1 cells. However, DHA at 5 μM had no lipolytic effect on differentiated 3T3-L1 cells, as assessed by no enhancement of glycerol release. Conclusions: These results demonstrate that DHA at 5 μM has a strong anti-adipogenic effect on differentiating 3T3-L1 cells through the reduced expression and phosphorylation of C/EBP-α, PPAR-γ, FAS, perilipin A, and STAT-3.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.312-318
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• 2023

The natural flavonoid macakurzin C (1) exhibited adiponectin biosynthesis-inducing activity during adipogenesis in human bone marrow mesenchymal stem cells and its molecular mechanism was directly associated with a pan-peroxisome proliferator-activated receptor (PPAR) modulator affecting all three PPAR subtypes α, γ, and δ. In this study, increases in adiponectin biosynthesis-inducing activity by macakurzin C derivatives (2-7) were studied. The most potent adiponectin biosynthesis-inducing compound 6, macakurzin C 3,5-dimethylether, was elucidated as a dual PPARα/γ modulator. Compound 6 may exhibit the most potent activity because of the antagonistic relationship between PPARδ and PPARγ. Docking studies revealed that the O-methylation of macakurzin C to generate compound 6 significantly disrupted PPARδ binding. Compound 6 has therapeutic potential in hypoadiponectinemia-related metabolic diseases.

• Korean Journal of Exercise Nutrition
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• v.13 no.2
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• pp.131-140
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• 2009

The aim of this study was to investigate the expression of PPAR-α, -β/δ, -γ, PGC-1α, GLUT-4 and p-AMPK-α₂ protein in the skeletal muscle of diabetic induced-rats by endurance training combined with rosiglitazone. The expression of PPAR-α, -β/δ, -γ, PGC-1α, GLUT-4 and p-AMPK-α₂ protein in red and white gastrocnemius by western blotting. The body weight was higher in diabetic induced-rats compared to the normal rats and after the treatment of exercise combined with rosiglitazone was significantly reduced in the all group. The levels of blood glucose was higher in diabetic induced-rats compared to the normal rats and after the treatment of exercise combined with rosiglitazone was significantly reduced in the all group. The expression of PPAR-α, -γ, PGC-1α in skeletal muscle of diabetic induced-rats were increased all groups and increased significantly in the group with exercise combined with rosiglitazone. The expression of GLUT-4 and p-AMPK-α₂ protein in the skeletal muscle of diabetic induced-rats were increased all groups and increased significantly in the group with exercise combined with rosiglitazoneI. These results suggest that exercise training and rosiglitazone may act as complementary therapies for the treatment of insulin rasistance.

• Journal of Ginseng Research
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• v.35 no.1
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• pp.45-51
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• 2011

Wild ginseng has been used as a traditional medicine for thousands of years and for increase physical strength in Korea, China and Japan. This study reports that cultivated wild ginseng (CWG) inhibits adipocyte differentiation of 3T3-L1 pre-adipocytes in a concentration-dependent manner. Inhibition of adipocyte differentiation is one possible anti-obesity strategy. CWG inhibits the expression of the adipocyte differentiation regulator peroxisome proliferators-activated receptor (PPAR)${\gamma}$ and CCAAT/enhancer-binding protein ${\alpha}$mRNA. It also inhibited the expression of PPAR${\gamma}$ and adiponectin at the protein level during the differentiation of pre-adipocytes into adipocytes. Additionally, CWG blocked the cell cycle at the sub-$G_1$ phase transition, causing cells to remain in the pre-adipocyte state. These results indicate that CWG inhibits adipocyte differentiation and adipogenesis through pre-adipocyte cell cycle arrest in cultured 3T3-L1 cells.

• Journal of Korean Medicine for Obesity Research
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• v.13 no.2
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• pp.74-83
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• 2013

Objectives: This study was performed to evaluate the effects of fermented lotus extracts on the inhibition of differentiation in 3T3-L1 preadipocytes. Methods: Extracts of lotus leaf and lotus root were fermented using 4 different probiotics separately, including Lactobacillus plantarum, Lactobacillus rhamnosus, Bifidobacterium breve, and Bifidobacterium longum. Inhibition of preadipocyte differentiation was examined by Oil red O dye staining. Expressions of adipogenic transcription factors including CCAAT/enhancer binding proteins (C/$EBP{\alpha}$) and peroxisome proliferators-activated receptor ${\gamma}$ ($PPAR{\gamma}$) were analyzed by real time polymerase chain reaction and Western blotting analysis. Results: Fermented lotus extracts inhibited adipogenic transcription factors by inhibiting preadipocytes differentiation. All of the groups fermented by 4 kinds of probiotics showed reduction in Oil Red O dye staining. Bifidobacterium breve showed the most effective inhibition of C/$EBP{\alpha}$. Bifidobacterium breve and Bifidobacterium longum showed the best downregulation of $PPAR{\gamma}$ expressions compared with the control and the unfermented lotus group. Conclusions: Fermented lotus extracts showed significant effects on inhibition of preadipocyte differentiation in 3T3-L1 preadipocytes showing correlation with insulin sensitivity and lipid metabolism related with obesity.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.96-103
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• 2012

Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated whether the Aloe QDM complex could improve metabolic disorders related to blood glucose levels and insulin resistance. Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of Aloe QDM complex or pioglitazone (PGZ) or metformin (Met) and were compared with unsupplemented controls (high-fat diet; HFD) or mice fed a regular diet (RD). RT-PCR and western blot analysis were used to quantify the expression of obesity-induced inflammation. Dietary Aloe QDM complex lowered body weight, fasting blood glucose, plasma insulin, and leptin levels, and markedly reduced the impairment of glucose tolerance in obese mice. Also, Aloe QDM complex significantly enhanced plasma adiponectin levels and insulin sensitivity via AMPK activity in muscles. At the same time, Aloe QDM decreased the mRNA and protein of $PPAR{\gamma}/LXR{\alpha}$ and scavenger receptors in white adipose tissue (WAT). Dietary Aloe QDM complex reduces obesity-induced glucose tolerance not only by suppressing $PPAR{\gamma}/LXR{\alpha}$ but also by enhancing AMPK activity in the WAT and muscles, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D.

• Biomolecules & Therapeutics
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• v.24 no.6
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• pp.650-658
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• 2016

Chronic alcohol consumption causes alcoholic liver disease, which is associated with the initiation of dysregulated lipid metabolism. Recent evidences suggest that dysregulated cholesterol metabolism plays an important role in the pathogenesis of alcoholic fatty liver disease. Ecklonia stolonifera (ES), a perennial brown marine alga that belongs to the family Laminariaceae, is rich in phlorotannins. Many studies have indicated that ES has extensive pharmacological effects, such as antioxidative, hepatoprotective, and antiinflammatory effects. However, only a few studies have investigated the protective effect of ES in alcoholic fatty liver. Male Sprague-Dawley rats were randomly divided into normal diet (ND) (fed a normal diet for 10 weeks) and ethanol diet (ED) groups. Rats in the ED group were fed a Lieber-DeCarli liquid diet (containing 5% ethanol) for 10 weeks and administered ES extract (50, 100, or 200 mg/kg/day), silymarin (100 mg/kg/day), or no treatment for 4 weeks. Each treatment group comprised of eight rats. The supplementation with ES resulted in decreased serum levels of triglycerides (TGs), total cholesterol, alanine aminotransferase, and aspartate aminotransferase. In addition, there were decreases in hepatic lipid and malondialdehyde levels. Changes in liver histology, as analyzed by Oil Red O staining, showed that the ES treatment suppressed adipogenesis. In addition, the ES treatment increased the expression of fatty acid oxidation-related genes (e.g., PPAR-${\alpha}$ and CPT-1) but decreased the expression of SREBP 1, which is a TG synthesis-related gene. These results suggest that ES extract may be useful in preventing fatty acid oxidation and reducing lipogenesis in ethanol-induced fatty liver.