• Journal of Applied Biological Chemistry
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• v.62 no.3
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• pp.229-237
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• 2019

More effective treatments are needed for non-alcoholic fatty liver disease (NAFLD). We hypothesized that water extracts of blackberry fruits (BF) and leaves (BL) and their combinations (BFL) reduce fat deposition in HepG2 cells and modulate shor-tchain fatty acids (SCFA) and fecal bacteria in vitro. HepG2 cells were treated with BF, BL, BFL1:2, and BFL1:3 for 1 h, and 0.5 mM palmitate was added to the cells. Moreover, low ($30{\mu}g/mL$) and high doses ($90{\mu}g/mL$) of BL and BF were applied to fecal bacteria in vitro, and SCFA was measured by GC. BL, BF, BFL1:2, and BFL1:3 reduced triglyceride deposition in the cells in a dose-dependent manner, and BFL1:2 and BFL1:3 had a stronger effect than BF. The content of malondialdehyde, an index of oxidative stress, was also reduced in BL, BF, and BFL1:2 with increasing superoxide dismutase and glutathione peroxidase activities. The mRNA expression of acetyl CoA carboxylase, fatty acid synthase, and sterol regulatory element-binding protein-1c was reduced in BL, BF, BFL1:2, and BFL1:3 compared to the control, and BFL1:2 had the strongest effect. By contrast, the carnitine palmitolytransferase-1expression, a regulator of fatty acid oxidation, increased mostly in BFL1:2 and BFL1:3. Tumor necrosis factor-${\alpha}$ and interleukin-$1{\beta}$ expression was reduced in BL compared to that in BF and BFL1:2 in HepG2 cells. Interestingly, BL increased propionate production, and BF increased butyrate and propionate production and increased total SCFA content in fecal incubation. BF increased the contents of Bifidobacteriales and Lactobacillales and decreased those of Clostridiales, whereas BL elevated the contents of Bacteroidales and decreased those of Enterobacteriales. In conclusion, BFL1:2 and BFL1:3 may be potential therapeutic candidates for NAFLD.

• Animal Bioscience
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• v.34 no.3_spc
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• pp.385-392
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• 2021

Objective: The present study was conducted to investigate the effects of lycopene on growth performance, abdominal fat deposition, serum lipids levels, activities of hepatic lipid metabolism related enzymes and genes expression in broiler chickens. Methods: A total of 256 healthy one-day-old male Arbor Acres broiler chicks were randomly divided into four groups with eight replicates of eight birds each. Birds were fed basal diet supplemented with 0 (control), 100, 200, and 400 mg/kg lycopene, respectively. Results: Dietary 100 mg/kg lycopene increased the body weight at 21 day of age compared to the control group (p<0.05). Compared to the basal diet, broilers fed diet with 100 mg/kg lycopene had decreased abdominal fat weight, and broilers fed diet with 100 and 200 mg/kg lycopene had decreased abdominal fat percentage (p<0.05). Compared to control, diets with 100, 200, and 400 mg/kg lycopene reduced the levels of total triglyceride and total cholesterol in serum, and diets with 100 and 200 mg/kg lycopene reduced the level of serum low density lipoprotein cholesterol (p<0.05). The activity of fatty acid synthase (FAS) in 400 mg/kg lycopene treated broilers and the activity of acetyl-CoA carboxylase (ACC) in 100, 200, and 400 mg/kg lycopene treated broilers were lower than those fed basal diet (p<0.05). Lycopene increased the mRNA abundance of adenosine monophosphate activated protein kinase α (AMPK-α), whereas decreased the mRNA abundance of sterol regulatory element-binding protein 1, FAS, and ACC compared to the control group (p<0.05). Conclusion: Dietary lycopene supplementation can alleviate abdominal fat deposition and decrease serum lipids levels, possibly through activating the AMPK signaling pathway, thereby regulating lipid metabolism such as lipogenesis. Therefore, lycopene or lycopene-rich plant materials might be added to poultry feed to regulate lipid metabolism.

• Journal of Life Science
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• v.27 no.2
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• pp.155-163
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• 2017

Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

• Journal of Life Science
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• v.29 no.9
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• pp.964-971
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• 2019

Hepatic lipid accumulation and insulin resistance increases in patients with non-alcoholic fatty liver disease. Piperine is a major compound found in black pepper (Piper nigrum) and long pepper (P. longum). Piperine has been used in fine chemical for its anti-cancer, anti-obesity, anti-diabetic, anti-inflammatory and anti-oxidant properties. However, the signaling-based mechanism of piperine and its role as an inhibitor of lipogenesis and insulin resistance in human hepatocyte cells remains ill-defined. In the present study, we explored the effects of piperine on lipid accumulation and insulin resistance, and explored the potential underlying molecular mechanisms in palmitate-treated HepG2 cells. Piperine treatment resulted in a significant reduction of triglyceride content. Furthermore, piperine treatment decreased palmitate-treated intracellular lipid deposition by inhibiting the lipogenic target genes, sterol-regulatory-element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS); whereas the expression of carnitine palmitoyl transferase (CPT-1) and phosphorylation of acetyl coenzyme A carboxylase (ACC) gene involved in fatty acid oxidation was increased. Moreover, piperine also inhibited the phosphorylation of insulin receptor substrate (IRS)-1 (Ser307). Piperine treatment modulated palmitate-treated lipid accumulation and insulin resistance in HepG2 cells with concomitant reduction of lipogenic target genes, such as SREBP-1 and FAS, and induction of CPT-1-ACC and phosphorylation of IRS-1 (Tyr632)-Akt pathways. Therefore, piperine represents a promising treatment for the prevention of lipid accumulation and insulin resistance.

• Korean Journal of Food Science and Technology
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• v.47 no.1
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• pp.111-118
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• 2015

In the present study, the phenolic compound level, antioxidant activity, and inhibition of lipid accumulation in Aspergillus oryzae-fermented water extracts of the Platycodon grandiflorum (PG) root and the Curcuma longa (CL) root were determined. Total polyphenol and flavonoid contents were decreased after fermentation. However, the flavonoid content of the fermented PG (FPG) was increased by 2.9-fold that of the PG before fermentation. In addition, the antioxidant activities were significantly decreased following fermentation. The potential anti-obesity activity was assessed by determining lipid accumulation and mRNA expression of sterol regulatory element-binding protein 1c (SREBP-1c) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) in 3T3-L1 cells. Aspergillus-fermented extracts of PG and CL roots decreased lipid accumulation, and mRNA expression of SREBP-1c and $PPAR{\gamma}$ in 3T3-L1 cells. These results indicate that Aspergillus fermentation augments the anti-obesity activity of PG and CL by regulating the expression of the genes involved in lipid accumulation and cell differentiation of 3T3-L1 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1126-1131
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• 2010

The antiobesity effect of soymilks fermented with Bacillus subtilis KC-3 (KCCM 42923) from cheonggukjang was compared with other sources of B. subtilis KCCM 11316 and B. subtilis MYCO. The antiobesity effect was investigated by measuring the release of leptin, Oil red O staining, glycerol secretions and adipogenic transcription factor by reverse transcription-polymerase chain reaction (RT-PCR) in the 3T3-L1 adipocytes. Fermented soymilk with B. subtilis KC-3 (F-KC) led to decrease levels of leptin secretion and increase levels of glycerol secretion in the cells. In addition, F-KC reduced contents of Oil red O dye in the 3T3-L1 adipocytes. Also, mRNA expression levels of both SREBP-1c (sterol regulatory element-binding protein 1-c) and PPAR-$\gamma$ (peroxisome proliferator-activated receptor-$\gamma$), which are adipogenic transcription factor, in cells treated with F-KC were markedly down regulated. These results demonstrate that the Bacillus subtillis fermented soymilk (F-KC) decreased lipid content in 3T3-L1 adipocytes by inhibiting lipogenesis. All B. subtilis fermented soymilks had shown antiobesity activities, however, F-KC exhibited the strongest antiobesity effect in the 3T3-L1 adipocytes. Our study suggests that especially F-KC increased the potential of antiobesity effects.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.6
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• pp.802-808
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• 2013

Here we tried to uncover the potential anti-lipogenic effect and the underlying mechanism of Phaseolus angularis seed in a cellular model of nonalcoholic fatty liver disease (NAFLD) induced in HepG2 cells. Ethanol extract of Phaseolus angularis seed (JSD) was prepared. HepG2 cells were incubated in palmitate containing media to induce intracellular lipid accumulation, and co-treated with JSD for 16 hrs before examine intracellular lipid content. In control group, the cells were not co-treated with JSD. We measured the effects of JSD on liver X receptor ${\alpha}$ ($LXR{\alpha}$) and sterol regulatory element-binding transcription factor-1c (SREBP-1c) expression, transcription level of lipogenic genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells. JSD markedly reduced palmitate-induced intracellular lipid accumulation in HepG2 cells. JSD suppressed $LXR{\alpha}$/SREBP-1c expression, and SREBP-1c mediated induction of ACC, FAS, and SCD-1. Furthermore, JSD activated AMPK, which plays a major role in the control of hepatic lipid metabolism. Taken together, it is suggested that JSD has a potential to alleviate hepatic steatosis, at least in part, by suppressing $LXR{\alpha}$/SREBP-1c mediated induction of lipogenic genes. In addtion, the anti-lipogenic potential may be associated with activation of AMPK. Therefore, the Phaseolus angularis seed could be applied as a potential therapeutics for NAFLD with additional clinical studies.

• Journal of Korean Medicine Rehabilitation
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• v.26 no.1
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• pp.13-31
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• 2016

Objectives In this study, it was investigated whether Gami-Handayeolso-Tang (HDYST) medication has anti-obesity effects in high fat diet (HFD)-fed obese mice. Methods The experimental animals were divided into five groups-normal diet-fed (ND), high fat diet-fed control (HFD), HFD+HDYST 150, HFD+HDYST 300, and HFD+orlistat as a positive drug. The obese markers such as body weight, diet efficiency ratio, serum levels of total cholesterol, triglyceride, lipid contents, leptin, adiponectin, and GOT/GPT were measured. Also, white adipose tissue, liver weight, abdominal fat mass, hepatic lipid contents, and mRNA expression of obese-associating genes were examined in obese mice. Results In high fat diet-fed mice, HDYST administration significantly decreased body weight, diet efficiency ratio, serum levels of total cholesterol, triglyceride, LDL-cholesterol, as well as leptin and GOT/GPT, compared to the HFD group in a dose-dependent manner. HDYST increased significantly the serum levels of HDL-cholesterol and adiponectin. It also reduced the accumulation of lipids, such as total lipid and triglycerides, in organs such as liver and abdominal adipose tissue. Moreover, HDYST administration significantly decreased the expression levels of fatty acid synthetic genes, such as sterol regulatory element-binding protein-1c (SREBP-1c), FAS and Stearoyl-Coenzyme A desaturase 1 (SCD-1), in the liver tissues, while it increased the messenger RAN (mRNA) levels of fatty acid catalytic genes, such as Peroxisome proliferator activated receptor alpha (PPAR-${\alpha}$), acyl-COA oxidase (ACO), and Carnitine palmitoyltransferase-1a (CPT-1a). Conclusions Based on the results above, HDYST reveals anti-obesity effects declining body fat accumulation through the regulation of fatty acid metabolism and leptin/adiponectin serum levels. It therefore suggests that HDYST can be clinically useful for the treatment of obesity.

• KSBB Journal
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• v.24 no.6
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• pp.549-555
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• 2009

4 kinds of Regional Special Natural Products (RSNPs), such as Anthrisci radix, Psoraleae semen, Siegesbeckiae herba and Corni fructus were examined to verify for anti-obesity effect. $PPAR\gamma$ (peroxisome proliferator-activated receptor $\gamma$) from 3T3-L1 cell concerning adipocyte differentiation was suppressed by different concentraton of 4 RSNPs with western blot, when treated RSNPs' extract and MDI (IBMX, Dexamethasone, Insulin) at the same time. Also, SREBP-1 (Sterol regulatory element binding protein) controlling lipogenesis and $PPAR\gamma$ expression levels were reduced by these 4 RSNPs' extract, when these chemicals after differentiation of 3T3-L1 cell. And lipid droplets were reduced by 7.5%, 14.4%, 18.3% and 30% at different concentration of Anthrisci radix from Oil Red O staining. Also, it was reduced by 2%, 4.9%, 9.3% and 38% at different concentration of Psoraleae semen. For Siegesbeckiae herba, it was inhibited by 1.4%, 6.4%, 16.4% and 30.1%, respectively. And Corni fructus was also showed by 0.9%, 6.3%, 13.7% and 33% at same concentration of Siegesbeckiae herba. These 4 kinds of RSNPs were expected for a useful material for anti-obesity materials.

• Journal of Korean Medicine for Obesity Research
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• v.15 no.2
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• pp.75-92
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• 2015

Objectives: This study was designed to investigate the effect of Gami-cheongpyesagan-tang extract (GCST) on high fat diet-induced obesity in rats. Methods: The mice were divided into six groups; normal diet control, high fat diet control (HFD), HFD+GCST administrated group (100, 200, and 400 mg/kg) and olistat-admistrated group. Obesity was induced by high fat diet (45%) for 7 weeks in mice, and GCST was administrated orally every day for 7 weeks. The body weight, food intake, and serological markers such as total cholesterol, triglyceride, lipid contents, leptin, adiponectin and glutamic oxaloacetic transaminase/glutamic pyruvic transaminase were measured in mice. The mRNA expression of obese-associating genes such as sterol regulatory element-binding protein (SREBP)-1c, fatty acid synthase (FAS), stearoyl-CaP desaturase (SCD-1), peroxisome proliferator-activated receptor $(PPAR)-{\alpha}$, COA oxidase (ACO), and carnitine palmitoyltransferase ($CPT-1{\alpha}$) was analyzed by reverse transcription polymerase chain reaction. Results: The administration of GCST at 400 mg/kg, significantly reduced the increase of body weight and food intake as well as food efficiency compared to HFD group. GCST decreased the serum levels of triglyceride, total cholesterol, low-density lipoprotein-cholesterol, leptin in HFD control group and inhibited lipid accumulation in liver and adipose tissues, but did not increase high-density lipoprotein-cholesterol. In the liver tissues of GCST administrated HFD group, the mRNA levels of SREBP-1c, FAS and SCD-1 were decreased and the mRNA levels of $PPAR-{\alpha}$, ACO, and $CPT-1{\alpha}$ were increased. Conclusions: These results indicate that GCST could improve high fat diet induced obesity through inhibiting the hyperlipidemia in fatty Liver. It suggest that GCST may be used clinically for declining the accumultion of body fat with hyperlipidemia.