• 동의생리병리학회지
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• 제27권6호
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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.

• 생명과학회지
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• 제27권2호
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• pp.155-163
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• 2017

상엽은 뽕나무 잎을 건조한 약재로서 항염증, 항당뇨, 미백, 항산화, 항박테리아, 항알러지 및 면역조절 등과 같은 여러 가지 약리작용을 하는 것으로 알려져 있으나 항비만 효능에 대한 연구는 부족한 실정이다. 본 연구에서는 상엽 에탄올 추출물(ethanol extracts of Mori Folium, EEMF)이 유발하는 항비만 효능을 확인하기 위하여 3T3-L1 지방전구세포가 지방세포로 분화되는 과정에서 EEMF가 어떠한 영향을 미치는 지를 조사하였다. 3T3-L1 지방전구세포의 분화유도 시 EEMF를 처리하였을 경우 지방세포의 특징인 지방방울의 수 및 지방함량이 농도의 존적으로 감소하였으며, triglyceride의 생성도 억제되는 것으로 나타났다. 또한 EEMF는 pro-adipogenic transcription factors인 SREBP-1c, $PPAR{\gamma}$, $C/EBP{\alpha}$ 및 $C/EBP{\beta}$ 의 발현억제와 함께 adipocyte-specific genes인 aP2 및 Leptin의 발현억제도 유발하는 것으로 조사되었다. 특히 EEMF는 AMPK 및 ACC의 인산화를 억제하는 것으로 나타났지만 AMPK 억제제인 compound C를 이용하여 AMPK의 활성을 억제하였을 경우 EEMF에 의하여 유발되는 pro-adipogenic transcription factors 및 adipocyte-specific genes의 억제현상이 회복되었다. 이상의 결과에서 EEMF가 유발하는 adipogenesis의 억제는 AMPK signaling pathway의 활성화를 통하여 유발된다는 것을 알 수 있었으며, 추가적인 연구를 통하여 상엽에 함유되어 있는 유효성분에 대한 분석이 필요할 것으로 생각된다.

• 대한한방내과학회지
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• 제35권1호
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• pp.70-78
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• 2014

Objectives : Hoechunyanggyeok-san (HYS) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory diseases. HYS has been reported to be a useful treatment for diabetes, atherosclerosis and hyperlipidemia in the type 1 diabetic model. However, the mechanism of the effects of HYS against hyperglycemia and hyperlipidemia is poorly understood. In the present study, we investigated the underlying mechanism of ameliorative effect of HYS on hyperglycemia and hyperlipidemia in vivo. Methods : HYS (10, 50 mg/kg/day, p.o.) was administered every day for 2 weeks to db/db mice and its effect was compared with vehicle-treated db/db mice. To confirm serum glucose and triglyceride (TG) changes, serological testing was performed. The levels of sterol regulatory element-binding protein-1 (SREBP-1) activity and Sirtuin1 (SIRT1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$) expression were analyzed by western blot analysis. Results : The administration of HYS significantly decreased the elevated serum glucose and TG in db/db mice. HYS administration increased the levels of SIRT1 and AMPK expression compared with the vehicle-treated group. Moreover, HYS treatment significantly inhibited SREBP-1 activity and $ACC{\alpha}$ expression in the liver, while the vehicle-treated group exhibited their increase. Conclusions : In conclusion, HYS is suggested to have an improvement effect on hyperglycemia and hyperlipidemia by activating the SIRT1/AMPK signaling pathway and inhibiting SREBP-1.

• Nutrition Research and Practice
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• 제11권3호
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• pp.180-189
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• 2017

BACKGROUND/OBJECTIVES: Recent living condition improvements, changes in dietary habits, and reductions in physical activity are contributing to an increase in metabolic syndrome symptoms including diabetes and obesity. Through such societal developments, humankind is continuously exposed to metabolic diseases such as diabetes, and the number of the victims is increasing. This study investigated Cordyceps militaris water extract (CMW)-induced glucose uptake in HepG2 cells and the effect of CMW treatment on glucose metabolism. MATERIALS/METHODS: Colorimetric assay kits were used to determine the glucokinase (GK) and pyruvate dehydrogenase (PDH) activities, glucose uptake, and glycogen content. Either RT-PCR or western blot analysis was performed for quantitation of glucose transporter 2 (GLUT2), hepatocyte nuclear factor 1 alpha ($HNF-1{\alpha}$), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phosphorylated AMP-activated protein kinase (pAMPK), phosphoenolpyruvate carboxykinase, GK, PDH, and glycogen synthase kinase 3 beta ($GSK-3{\beta}$) expression levels. The ${\alpha}-glucosidase$ inhibitory activities of acarbose and CMW were evaluated by absorbance measurement. RESULTS: CMW induced glucose uptake in HepG2 cells by increasing GLUT2 through $HNF-1{\alpha}$ expression stimulation. Glucose in the cells increased the CMW-induced phosphorylation of AMPK. In turn, glycolysis was stimulated, and glyconeogenesis was inhibited. Furthermore, by studying the mechanism of action of PI3k, Akt, and $GSK-3{\beta}$, and measuring glycogen content, the study confirmed that the glucose was stored in the liver as glycogen. Finally, CMW resulted in a higher level of ${\alpha}-glucosidase$ inhibitory activity than that from acarbose. CONCLUSION: CMW induced the uptake of glucose into HepG2 cells, as well, it induced metabolism of the absorbed glucose. It is concluded that CMW is a candidate or potential use in diabetes prevention and treatment.

• 동의생리병리학회지
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• 제31권3호
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• pp.159-166
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• 2017

Through this study, the authors investigated the anti-steatosis effects of the Amomum cardamomum ethyl acetate fraction in free fatty acids (FFAs)-induced human hepatocellular carcinoma HepG2 cells. The ethyl acetate fraction of Amomum cardamomum (ACEA) was extracted with 70% ethanol and then the extract was evaporated using a rotary evaporator prior to sequential fractionation. Human hepatocellular carcinoma were treated with different concentrations of ACEA in the presence and absence of FFAs. To demonstrate the reactive oxygen species (ROS) scavenging activity, DCFDA level was analyzed by using in vitro assay system. Cell viability, lipid accumulation, intracellular triglycerides, malondialdehyde (MDA), liver steatosis related signaling molecules and inflammatory cytokines such as interleukin (IL)-6, 8, tumor necrosis factor-alpha ($TNF-{\alpha}$) were also investigated. As results, ACEA inhibited the FFAs-induced ROS, lipid accumulation, intracellular triglycerides, and MDA in a dose dependent manner. Treatment of human hepatocellular cells with ACEA induced the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and carnitine palmitoyltransferase I (CPT1) expression using western blot analysis. ACEA also potently suppressed the FFAs-induced inflammatory cytokines including IL-6, IL-8 and $TNF-{\alpha}$. These results suggest that the ethyl acetate fraction of Amomum cardamoum extract own inhibitory effects of liver steatosis by inhibiting ROS, lipid accumulation, intracellular triglycerides, MDA through AMPK signaling and anti-inflammatory actions.

• 사상체질의학회지
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• 제29권2호
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• pp.154-173
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• 2017

Objectives This study was conducted to evaluate the effects of Yeoldahanso-tang on obesity in rats induced by high fat diet experimentally. Methods The experiment was conducted with rats divided into 5 groups. Rats were evaluated for change of weight, hematologic and serum biochemical parameters. Results Yeoldahanso-tang group showed significant reductions in FER, body weight, adipose tissue weight and size. The level of Creatinine, glucose, ALP, T-cholesterol, Triglyceride, LDL-cholesterol, Leptin and IGF-1 of Yeoldahanso-tang group was significantly lower than those in HFD-CTL group. The level of HDL-cholesterol, free fatty acid and Adiponectin in Yeoldahanso-tang group was significantly higher than those in HFD-CTL group. As compared with HFD-CTL group, AMPK-${\alpha}1$, UCP2 and adiponectin mRNA in liver of Yeoldahanso-tang group were significantly increased and AP2/FABP4, AMPK-${\alpha}2$ and PPAR-${\gamma}$ mRNA in liver of Yeoldahanso-tang group was significantly decreased. Conclusion These results suggest that Yeoldahanso-tang has inhibitory effects on obesity in high fat diet induced obese mice.

• 대한예방한의학회지
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• 제22권2호
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• pp.77-107
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• 2018

Objectives : In present study, therefore, possible beneficial pharmacological activities of standard potato protein extracts (SPE) were observed on the mild diabetic obese mice. Methods : After end of 12 weeks of continuous oral administrations of three different dosages of SPE 400, 200 and 100 mg/kg, or metformin 250 mg/kg, analyzed the hepatoprotective, hypolipidemic, hypoglycemic, nephroprotective and anti-obesity effects, separately. In addition, liver antioxidant defense systems were additionally measured with lipid metabolism-related genes expressions and hepatic glucose-regulating enzyme activities for action mechanism. Results : All of diabetes and related complications including obesity were significantly inhibited by treatment of SPE 400, 200 and 100 mg/kg, dose-dependently, and they also dramatically normalized the hepatic lipid peroxidation and depletion of liver endogenous antioxidant defense system, the changes of the hepatic glucose-regulating enzyme activities, also changes of the lipid metabolism-related genes expressions including hepatic $AMPK{\alpha}1$ and $AMPK{\alpha}2$ mRNA expressions, dose-dependently. Especially, SPE 200 mg/kg constantly showed favorable inhibitory activities against type II diabetes and related complications as comparable to those of metformin 250 mg/kg in HFD mice, respectively. Conclusions : The present work demonstrated that SPE 400, 200 and 100 mg/kg showed favorable anti-diabetic and related complications including obesity refinement activities in HFD mice, through AMPK upregulation mediated hepatic glucose enzyme activity and lipid metabolism-related genes expression, antioxidant defense system and pancreatic lipid digestion enzyme modulatory activities.

• IMMUNE NETWORK
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• 제11권2호
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• pp.107-113
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• 2011

Background: Metabolic disorders, including type II diabetes and obesity, present major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has become the focus of a great deal of attention as a novel therapeutic target for the treatment of metabolic syndromes. In this study, we evaluated whether dietary aloe could reduce obesity-induced inflammation and adipogenesis. Methods: Male C57BL/6 obese mice fed a high-fat diet for 54 days received a supplement of aloe formula (PAG, ALS, Aloe QDM, and Aloe QDM complex) or pioglitazone (PGZ) 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. Results: Aloe QDM complex downregulated fat size through suppressed expression of scavenger receptors on adipose tissue macrophages (ATMs) compared with HFD. Both white adipose tissue (WATs) and muscle exhibited increased AMPK activation through aloe supplementation, and in particular, the Aloe QDM complex. Obesity-induced inflammatory cytokines (IL-$1{\beta}$ and -6) and $HIF1{\alpha}$ mRNA and protein were decreased markedly, as was macrophage infiltration by the Aloe QDM complex. Further, the Aloe QDM complex decreased the translocation of NF-${\kappa}B$ p65 from the cytosol in the WAT. Conclusion: Dietary aloe formula reduced obesity-induced inflammatory responses by activation of AMPK in muscle and suppression of proinflammatory cytokines in the WAT. Additionally, the expression of scavenger receptors in the ATM and activation of AMPK in WAT led to reduction in the percent of body fat. Thus, we suggest that the effect of the Aloe QDM complex in the WAT and muscle are related to activation of AMPK and its use as a nutritional intervention against T2D and obesity-related inflammation.

• 한방비만학회지
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• 제23권2호
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• pp.60-68
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• 2023

Objectives: This study was conducted to compare the effects of Hominis placenta (Jahage, J) and wild ginseng (SanSam, S) pharmacopuncture drugs on muscle differentiation and energy metabolism regulation in C2C12 myotubes. Methods: The C2C12 myoblasts were differentiated into myotubes for 5 days by replacing in medium containing 2% horse serum and then treated with J and S pharmacopuncture extract at different concentrations for 24 hr. The expression of myosin heavy chain and energy metabolism-regulating factors, myosin heavy chain (MHC), nuclear respiratory factor-1 (NRF-1), and proliferator-activated receptor γ coactivator-1 alpha (PGC-1α) were determined in C2C12 myotubes by western blot. Additionally, the phosphorylation of AMPK and the expression of mitochondrial biogenesis, including sirtuin 1 (SIRT1) were determined in the myotubes. Results: As a result, treatment with J and S pharmacopuncture extract at 0.1 and 1 mg/mL increased the MHC expression in C2C12 myotubes compared with non-treated cells, but only S pharmacopuncture was shown a significant and distinct increase in the expression. Expression of TFAM and NRF-1 was also shown significant increases in S and J pharmacopuncture in C2C12 myotubes compared to non-treated cells. The phosphorylation of AMPK and the expression of PGC-1α and SIRT1 showed increased expression in S and J pharmacopuncture compared to non-treated cells. The effect of low-dose of J pharmacopuncture on the phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and PGC-1α expression was greater than that of S pharmacopuncture. Conclusions: In conclusion, both J and S pharmacopuncture promote muscle differentiation in C2C12 myoblasts into myotubes and energy metabolism through the AMPK/SIRT1 signaling pathway. This indicates that the pharmacopuncture with tonic herbal medicines can help to improve skeletal muscle function.

• Journal of Animal Science and Technology
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• 제64권6호
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• pp.1199-1214
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• 2022

Apolipoprotein H (APOH) primarily engages in fat metabolism and inflammatory disease response. This study aimed to investigate the effects of APOH on fat synthesis in duck myoblasts (CS2s) by APOH overexpression and knockdown. CS2s overexpressing APOH showed enhanced triglyceride (TG) and cholesterol (CHOL) contents and elevated the mRNA and protein expression of AKT serine/threonine kinase 1 (AKT1), ELOVL fatty acid elongase 6 (ELOVL6), and acetyl-CoA carboxylase 1 (ACC1) while reducing the expression of protein kinase AMP-activated catalytic subunit alpha 1 (AMPK), peroxisome proliferator activated receptor gamma (PPARG), acyl-CoA synthetase long chain family member 1 (ACSL1), and lipoprotein lipase (LPL). The results showed that knockdown of APOH in CS2s reduced the content of TG and CHOL, reduced the expression of ACC1, ELOVL6, and AKT1, and increased the gene and protein expression of PPARG, LPL, ACSL1, and AMPK. Our results showed that APOH affected lipid deposition in myoblasts by inhibiting fatty acid beta-oxidation and promoting fatty acid biosynthesis by regulating the expression of the AKT/AMPK pathway. This study provides the necessary basic information for the role of APOH in fat accumulation in duck myoblasts for the first time and enables researchers to study the genes related to fat deposition in meat ducks in a new direction.