• 대한한의학방제학회지
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• 제25권4호
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• pp.457-469
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• 2017

Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

• 약학회지
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• 제53권5호
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• pp.286-292
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• 2009

In this study, we investigated the anti-obese activity of HPJ extract in C57BL/6J mice. The C57BL/6J mice were randomly divided into five groups: normal control group (Con), high fat diet control group (HFD), treatment groups with HPJ at 125 mg/kg (HPJ125), 250 mg/kg (HPJ250), or 500 mg/kg (HPJ500). To induce an obesity, mice were fed by a high fat diet for 6 weeks, and mice were administered with HPJ extract once a day for 8 weeks. At the end of treatment, we examined the effect of HPJ extract on body weight, plasma lipid, and lipogenic enzymes. HPJ extract was found to lower whole body and epididymal adipose tissue weights and lowered plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), non-esterified fatty acid (NEFA) and leptin, compared to those in HFD group. Histological analyses of the liver and fat tissues of mice treated with HPJ extract revealed significantly decreased number of lipid droplets and decreased size of adipocytes compared to the HFD group. In addition, HPJ extract preserved the morphological integrity of pancreatic islets. To elucidate an action mechanism of HPJ extract, Western blot and RT-PCR were performed using epididymal adipose tissues. HPJ extract up-regulated the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylasse (ACC). HPJ extract also attenuated lipogenic gene expressions of sterol regulatory element-binding protein $1{\alpha}$ (SREBP$1{\alpha}$), fatty acid synthase (FAS), sterol-CoA desaturase 1 (SCD1) and glycerol-3-phosphate acyltransferase (GPAT) in dose-dependent manners. In contrast, expressions of lipolytic genes such as peroxisome proliferator-activated receptor-$\alpha$ (PPAR-${\alpha}$) and CD36, and fatty acid $\beta$-oxidation gene, carnitine palmitoyltransferase-1 (CPT-1) were increased. These results suggest that HPJ extract ameliorates obesity through inhibiting synthesis of lipogenic enzymes as well as stimulating fatty acid oxidation resulting from activation of AMPK, and HPJ extract could be developed as a potential therapeutic agent for obese patients.

• 대한본초학회지
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• 제35권5호
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• pp.23-31
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• 2020

Objectives : This study was conducted to evaluate the anti-hyperlipidemia effect of Scutellariae Radix, Aucklandiae Radix and Bupleuri Radix(SAB). Methods : FL83B cells were mouse liver hepatocytes, and we used this cell line. FL83B cells were treated with 0.5 mM oleic acid(OA) for 24 h, SAB extract was treated. After OA treatment, intracellular triglyceride (TG) and free fatty acid contents were measured with AdiopoRed™ assay and Free Fatty Acid Quantitation assay kit, respectively. Further, we evaluated several lipogenesis and metabolic markers such as sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy3-methyl-glutaryl CoA reductase (HMGCR), hormone-sensitive lipase (HSL), carnitine palmitoyltransferase (CPT-1), peroxisome proliferator activated receptor alpha (PPARα), and cluster of differentiation (CD36) using RT-PCR and Western-blot analysis. Results : OA markedly increased intracellular TG and free fatty acid, which plays a key role in reducing hepatic lipid accumulation, in FL83B cells. These increases were alleviated by SAB extract. The mRNA and protein expression of Fatty acid(FA) oxidation factors (CPT-1, PPARα), lipolysis factor(HSL), FA transporter(CD36), cholesterol synthesis factors (HMGCoA) and Lipodenesis (SREBP-1c, FAS, and ACC-1) were significantly increased by treatment of SAB extract in the OA-induced fatty liver cell model. Conclusions : In summary, the treat of SAB extract showed a significant reduction of the influx of fatty acids into hepatocytes, promoted the oxidation of fatty acids, and regulated fat synthesis-related factors, thereby regulating the accumulation of TG and free fatty acids.

• Animal Bioscience
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• 제35권5호
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• pp.763-777
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• 2022

Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms. Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot. Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL-2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis. Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

• Nutrition Research and Practice
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• 제14권6호
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• pp.568-579
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• 2020

BACKGROUD/OBJECTIVES: Hepatic steatosis is the most common liver disorder, particularly in postmenopausal women. This study investigated the protective effects of standardized rice bran extract (RBS) on ovariectomized (OVX)-induced hepatic steatosis in rats. MATERIALS/METHODS: HepG2 cells were incubated with 200 µM oleic acid to induce lipid accumulation with or without RBS and γ-oryzanol. OVX rats were separated into three groups and fed a normal diet (ND) or the ND containing 17β-estradiol (E2; 10 ㎍/kg) and RBS (500 mg/kg) for 16 weeks. RESULTS: RBS supplementation improved serum triglyceride and free fatty acid levels in OVX rats. Histological analysis showed that RBS significantly attenuated hepatic fat accumulation and decreased hepatic lipid, total cholesterol, and triglyceride levels. Additionally, RBS suppressed the estrogen deficiency-induced upregulation of lipogenic genes, such as sterol regulatory element-binding protein 1 (SREBP1), acetyl-CoA carboxylase 1, fatty acid synthase, glycerol-3-phosphate acyltransferase, and stearoyl-CoA desaturase 1. CONCLUSIONS: RBS and γ-oryzanol effectively reduced lipid accumulation in a HepG2 cell hepatic steatosis model. RBS improves OVX-induced hepatic steatosis by regulating the SREBP1-mediated activation of lipogenic genes, suggesting the benefits of RBS in preventing fatty liver in postmenopausal women.

• Nutrition Research and Practice
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• 제10권6호
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• pp.575-582
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• 2016

BACKGROUNG/OBJECTIVES: The study was performed to investigate the effects and mechanisms of action of high maysin corn silk extract on body weight and fat deposition in experimental animals. MATERIALS/METHODS: A total of 30 male C57BL/6J mice, 4-weeks-old, were purchased and divided into three groups by weight using a randomized block design. The normal-fat (NF) group received 7% fat (diet weight basis), the high-fat (HF) group received 25% fat and 0.5% cholesterol, and the high-fat corn silk (HFCS) group received high-fat diet and high maysin corn silk extract at 100 mg/kg body weight through daily oral administration. Body weight and body fat were measured, and mRNA expression levels of proteins involved in adipocyte differentiation, fat accumulation, fat synthesis, lipolysis, and fat oxidation in adipose tissue and the liver were measured. RESULTS: After experimental diet intake for 8 weeks, body weight was significantly lower in the HFCS group compared to the HF group (P < 0.05), and kidney fat and epididymal fat pad weights were significantly lower in the HFCS group compared to the HF group (P < 0.05). In the HFCS group, CCAAT/enhancer binding protein-${\beta}$, peroxisome proliferator-activated receptor-${\gamma}1$ (PPAR-${\gamma}1$), and PPAR-${\gamma}2$ mRNA expression levels were significantly reduced (P < 0.05) in the epididymal fat pad, whereas cluster of differentiation 36, lipoprotein lipase, acetyl-CoA carboxylase-1, sterol regulatory element binding protein-1c, pyruvate dehydrogenase kinase, isozyme-4, glucose-6-phosphate dehydrogenase, and stearoyl-CoA desaturase-1 mRNA expression levels were significantly decreased in liver and adipose tissues (P < 0.05). In the HFCS group, mRNA expression levels of AMP-activated protein kinase, hormone-sensitive lipase, and carnitine palmitoyltransferase-1 were elevated (P < 0.05). CONCLUSIONS: It can be concluded that high maysin corn silk extract inhibits expression of genes involved in adipocyte differentiation, fat accumulation, and fat synthesis as well as promotes expression of genes involved in lipolysis and fat oxidation, further inhibiting body fat accumulation and body weight elevation in experimental animals.

• Asian-Australasian Journal of Animal Sciences
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• 제31권8호
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• pp.1088-1097
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• 2018

Objective: It is commonly accepted that adiponectin binds to its two receptors to regulate fatty acid metabolism in adipocytes. To better understand their functions in the regulation of intramuscular adipogenesis in goats, we cloned the three genes (adiponectin [AdipoQ], adiponectin receptor 1 [AdipoR1], and AdipoR2) encoding these proteins and detected their mRNA distribution in different tissues. We also determined the role of AdipoQ in the adipogenic differentiation of goat skeletal muscle satellite cells (SMSCs). Methods: SMSCs were isolated using 1 mg/mL Pronase E from the longissimus dorsi muscles of 3-day-old female Nanjiang brown goats. Adipogenic differentiation was induced in satellite cells by transferring the cells to Dulbecco's modified Eagle's medium supplemented with an isobutylmethylxanthine, dexamethasone and insulin cocktail. The pEGFP-N1-AD plasmid was transfected into SMSCs using Lipofectamine 2000. Expression of adiponectin in tissues and SMSCs was detected by quantitative polymerase chain reaction and immunocytochemical staining. Results: The three genes were predominantly expressed in adipose and skeletal muscle tissues. According to fluorescence and immunocytochemical analyses, adiponectin protein expression was only observed in the cytoplasm, suggesting that adiponectin is localized to the cytoplasm of goat SMSCs. In SMSCs overexpressing the AdipoQ gene, adiponectin promoted SMSC differentiation into adipocytes and significantly (p<0.05) up-regulated expression of AdipoR2, acetyl-CoA carboxylase, fatty-acid synthase, and sterol regulatory element-binding protein-1, though expression of CCAAT/enhancer-binding $protein-{\alpha}$, peroxisome proliferator-activated receptor ${\gamma}$, and AdipoR1 did not change significantly. Conclusion: Adiponectin induced SMSC differentiation into adipocytes, indicating that adiponectin may promote intramuscular adipogenesis in goat SMSC.

• 한국식품영양과학회지
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• 제43권6호
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• pp.822-828
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• 2014

본 연구에서는 3T3-L1 지방전구세포를 이용하여 Allium 속 식물의 하나인 참산부추(ASM) 메탄올 추출물의 ROS 생성 저해 및 지질 축적 억제 효과를 확인하고자 하였다. 먼저 ASM 메탄올 추출물 $100{\sim}2,000{\mu}g/mL$의 모든 농도에서 유의적인 DPPH 라디칼 소거능을 나타내었으며, 지방전구세포에 ASM 메탄올 추출물 $10{\sim}100{\mu}g/mL$를 처리하였을 때 세포 독성을 나타내지 않았다. 지방세포 내 ROS 관련 효소와 분화 관련 전사인자의 조절로 인한 중성지방 축적 저해 활성을 확인하기 위하여 지방전구세포를 분화 유도하면서 추출물을 농도별(10, 50, $100{\mu}g/mL$)로 처리하였다. 그 결과 ASM 메탄올 추출물은 대조군에 비해 ROS 생성량과 ROS 관련 효소인 G6PDH mRNA 발현을 농도 의존적으로 감소시켰다. 또한 ASM 메탄올 추출물에 의하여 지방세포 내 중성지방 축적량이 유의적으로 감소하였으며, 지방세포 분화에 관련된 전사인자인 SREBP1c, $PPAR{\gamma}$ 및 $C/EBP{\alpha}$ mRNA 발현도 유의적으로 감소하였다. 이상의 결과들로 볼 때 ASM 메탄올 추출물로 인한 ROS 생성 저해와 지질 축적 억제는 ROS 생성 및 ROS 관련 유전자의 발현감소로 인한 지방 생성 주요 전사인자의 유전자 발현 억제로 인한 것으로 보이며, ASM이 항비만 효과가 있는 천연물 소재로 개발 가능성이 있을 것으로 사료된다.

• 한국약용작물학회지
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• 제28권4호
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• pp.276-286
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• 2020

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.

• 한방재활의학과학회지
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• 제32권4호
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• pp.1-8
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• 2022

Objectives This study is to investigate the effects and mechanisms of Gastrodia elata extract (GEE) on the high-fat diet-induced obesity model. Methods C57BL/6 mice were randomly assigned into 5 groups (n=10). Control group was fed normal diet (ND). Obesity group was fed 60% high fat diet (HFD). The other three groups were fed HFD with 100, 200, 500 mg/kg GEE. After five weeks, body weight, liver and epididymal fat weight, triglyceride concentration in liver and serum, sterol regulatory element-binding protein-1 (SREBP-1), acetyl-CoA carboxylase (ACC), fatty acid synthase, peroxisome proliferator-activated receptor 𝛾 (PPAR-𝛾), CCAAT/enhancer binding protein 𝛼 (C/EBP-𝛼) expression level, insulin concentration in serum were measured. Results The GEE (100, 200, and 500 mg/kg)-treated animals exhibited substantial decreases in body mass, liver weight and epididymal white adipose tissue collate to the HFD-fed group. GEE treatment also reduced hepatic and serum triglyceride level. Furthermore, GEE treatment significantly inhibited adipogenesis in the GEE group by reducing the protein expression of SREBP-1, ACC and the messenger RNA expression of PPAR𝛾, C/EBP-𝛼, which are adipocyte differentiation-related genes. Conclusions These research outcomes recommend that GEE is possibly valuable for the prevention of HFD-induced obesity via modification of various pathways related with adipogenesis and adipocyte differentiation.