• Title/Summary/Keyword: steatosis model

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The Effect of Alisma orientale Extract on Free Fatty Acid-induced Lipoapoptosis in HepG2 Cells (택사(澤瀉)가 유리지방산으로 유발된 HepG2 cell의 lipoapoptosis에 미치는 영향)

  • Kim, Eun-Young;Lee, Jang-Hoon
    • The Journal of Internal Korean Medicine
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    • v.35 no.2
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    • pp.184-194
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    • 2014
  • Objectives : This study was designed to investigate the effect on lipoapoptosis of Alisma orientale extract against free fatty acid-induced cellular injury. Methods : HepG2 cells were used in an vitro model. HepG2 cells were treated with free fatty acids to generate a cellular model of nonalcoholic fatty liver disease (NAFLD). Using this cellular model, the anti-apoptotic effect and reducing steatosis of Alisma orientale extract against free fatty acid-induced cellular injury was evaluated by measuring steatosis and apoptosis. Results : Alisma orientale extract significantly attenuated free fatty acid-induced intracellular steatosis. Alisma orientale extract inhibited free fatty acid-mediated activation of pJNK, PUMA, BAX, caspase-3, and -9, and apoptotic kinases that are correlated with NAFLD. Alisma orientale extract also promoted Bcl-2, a anti-apoptotic protein. Conclusions : From the above, the Alisma orientale extract decreased the hepatocyte steatosis and showed the hepatocelluar protective effect by the regulation of apoptosis-related protein. It proposes the possibility of Alisma orientale extract to the treatment of nonalcoholic fatty liver disease in clinics.

Beakdugu-tang, Traditional Korean Digestant Medicine, Inhibits Hepatic Steatosis in Insulin Resistance Cell Model with HepG2 and THP-1

  • Kim, Hyuck;Lim, Dong-Woo;Park, Sung Yun;Park, Sun-Dong;Park, Won-Hwan;Kim, Jai-Eun
    • The Journal of Korean Medicine
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    • v.38 no.2
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    • pp.53-60
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    • 2017
  • Objectives: Beakdugu-tang (BDGT) consists of three medicinal herbs, and this prescription has long been used in treatment of various digestant problem in Korea. In this study, we designed to clarify mechanisms by which Korean traditional digestive medicine, BDGT, may exert anti-hepatic steatosis effects via improved insulin resistance cell model in human hepatocellular carcinoma (HepG2) and monocyte (THP-1). Materials and methods: The preparation of BDGT and constituents were extracted with 70% ethanol. HepG2 and THP-1 were treated with different concentrations of BDGT and constituents in the presence and absence of stimulants such as free fatty acids (FFAs) and oxidized low-density lipoprotein (ox-LDL), respectively. Results: The BDGT and its constituents inhibited the FFAs-stimulated lipid accumulation in HepG2 cells. Ethanol extracts of Amomum cardamomum (ACE) improved the ox-LDL induced insulin resistance in THP-1 cells. Also, treatment of monocytic cells with ACE increased anti-hepatic steatosis related gene levels including ABCA, ABCG and SR-B1. Conclusion: The results suggest that the ethanol extract of BDGT and its constituents potently inhibit the FFAs- and ox-LDL induced liver steatosis via improved insulin resistance.

Dietary carnosic acid suppresses hepatic steatosis formation via regulation of hepatic fatty acid metabolism in high-fat diet-fed mice

  • Park, Mi-Young;Mun, Seong Taek
    • Nutrition Research and Practice
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    • v.7 no.4
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    • pp.294-301
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    • 2013
  • In this study, we examined the hepatic anti-steatosis activity of carnosic acid (CA), a phenolic compound of rosemary (Rosmarinus officinalis) leaves, as well as its possible mechanism of action, in a high-fat diet (HFD)-fed mice model. Mice were fed a HFD, or a HFD supplemented with 0.01% (w/w) CA or 0.02% (w/w) CA, for a period of 12 weeks, after which changes in body weight, blood lipid profiles, and fatty acid mechanism markers were evaluated. The 0.02% (w/w) CA diet resulted in a marked decline in steatosis grade, as well as in homeostasis model assessment of insulin resistance (HOMA-IR) index values, intraperitoneal glucose tolerance test (IGTT) results, body weight gain, liver weight, and blood lipid levels (P < 0.05). The expression level of hepatic lipogenic genes, such as sterol regulating element binding protein-1c (SREBP-1c), liver-fatty acid binding protein (L-FABP), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase (FAS), was significantly lower in mice fed 0.01% (w/w) CA and 0.02% (w/w) CA diets than that in the HFD group; on the other hand, the expression level of ${\beta}$-oxidation-related genes, such as peroxisome proliferator-activated receptor ${\alpha}$ (PPAR-${\alpha}$), carnitine palmitoyltransferase 1 (CPT-1), and acyl-CoA oxidase (ACO), was higher in mice fed a 0.02% (w/w) CA diet, than that in the HFD group (P < 0.05). In addition, the hepatic content of palmitic acid (C16:0), palmitoleic acid (C16:1), and oleic acid (C18:1) was significantly lower in mice fed the 0.02% (w/w) CA diet than that in the HFD group (P < 0.05). These results suggest that orally administered CA suppressed HFD-induced hepatic steatosis and fatty liver-related metabolic disorders through decrease of de novo lipogenesis and fatty acid elongation and increase of fatty acid ${\beta}$-oxidation in mice.

Hepatoprotective effect of cordycepin-enriched Cordyceps militaris extract powder on high fat diet-induced hepatic steatosis in obese (ob/ob) mice

  • Ju-Hye Kim;Heejin Park;Mun-Hyoung Bae;Youngha Seo;Eun-Young Gu;Taek-Keun Oh;Byoung-Seok Lee
    • Korean Journal of Agricultural Science
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    • v.51 no.2
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    • pp.159-167
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    • 2024
  • Herbal medicinal mushroom Cordyceps militaris has been traditionally used as tonic medicine for metabolic syndrome. Cordycepin, main extract of C. militaris, has been reported with immunomodulatory, anticancer, and hepatoprotective effects. This study was conducted to evaluate the potential hepatoprotective effect of cordycepin-enriched Cordyceps militaris, against high fat diet (HFD)-induced hepatic steatosis (HS) in male obese (ob/ob) mice. HFD was provided to ob/ob mice ad libitum (except negative control). Cordycepin-enriched C. militaris extract powder (CM) was orally administered once daily at dose levels of 0, 125, 250, and 500 mg·kg-1 for 4 weeks. During the study, body weight gain was statistically increased in all HFD fed groups compared to negative control, but body weight gain in CM 500 mg·kg-1 treated group shows a low tendency compared to HS model group. In organ weights, absolute and relative weights (to body weight) in liver and perirenal adipose tissue were increased in all HFD treated groups except CM 500 mg·kg-1 treated group compared to the negative control. In clinical chemistry, serum glucose and total cholesterol levels in CM 250 and/or 500 mg·kg-1 treated groups were lower than HS model group. In microscopical examination, hepatocyte vacuolation with macrovesicles in HS model group was increased compared to negative control, but this finding was decreased in CM 500 mg·kg-1 treated group compared to HS model group. In this study, CM exhibited hepatoprotective effects against hepatic steatosis at mg·kg-1 in ob/ob mice.

Liver PPAR${\alpha}$ and UCP2 are Involved in the Regulation of Ovariectomy-Induced Adiposity and Steatosis by Swim Training

  • Jeong, Sun-Hyo;Yoon, Mi-Chung
    • Biomedical Science Letters
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    • v.16 no.4
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    • pp.239-246
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    • 2010
  • It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor ${\alpha}$ (PPAR${\alpha}$) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPAR${\alpha}$ and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPAR${\alpha}$ and its target genes responsible for peroxisomal fatty acid ${\beta}$-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPAR${\alpha}$ and UCP2 in female obese mice.

Quantitative analysis of lipid hydroperoxides levels in peripheral organs of Juvenile Visceral Steatosis (JVS) Mice at 1 month of age

  • Seiichi Matsugo;Miki Saito;Fumihiko Yasui;Kazuo Sasaki;Li, Meng-Xian;Masahisa Horiuchi;Takeyori Saheki
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.415-417
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    • 2002
  • Juvenile visceral steatosis (JVS) mouse is an animal model of the systemic camitine deficiency. JVS mice first develop fatty liver following cardiac hypertrophy. hyperammonemia, etc. To clarify the relationship between fatty liver and other symptoms. lipid hydroperoxides levels of peripheral oragans in JVS mice at 1 month were determined by the use of phosphine derivatives. We also report here a new method to quantitate the lipid components level in fatty liver of JVS mice.

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Histological Analysis of Hepatic Steatosis, Inflammation, and Fibrosis in Ascorbic Acid-Treated Ovariectomized Mice

  • Lee, Mijeong;Jeon, Suyeon;Lee, Jungu;Lee, Dongju;Yoon, Michung
    • Biomedical Science Letters
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    • v.28 no.2
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    • pp.101-108
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    • 2022
  • High-fat diet (HFD)-fed ovariectomized (OVX) female mice were used as an animal model of obese postmenopausal women. We investigated the effects of ascorbic acid on the histological changes induced in the liver. Plasma alanine aminotransferase levels and liver weights were higher in mice fed an HFD for 18 weeks than in mice fed a low-fat diet, effects that were inhibited by ascorbic acid. Similarly, mice fed an ascorbic acid-supplemented HFD had less hepatic lipid accumulation than did mice fed an HFD alone. Moreover, administration of ascorbic acid reduced inflammatory cells, including mast cells and CD68-positive cells, and inflammatory foci in the liver and inhibited hepatocyte ballooning. Hepatic collagen levels were lower in ascorbic acid-treated versus non-treated mice. These results suggest that ascorbic acid inhibits hepatic steatosis, inflammation, and fibrosis in obese OVX mice. Thus, ascorbic acid intake may be useful for postmenopausal women with nonalcoholic fatty liver disease.

Standardized rice bran extract improves hepatic steatosis in HepG2 cells and ovariectomized rats

  • Lim, Dong Wook;Jeon, Hyejin;Kim, Minji;Yoon, Minseok;Jung, Jonghoon;Kwon, Sangoh;Cho, Suengmok;Um, Min Young
    • Nutrition Research and Practice
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    • v.14 no.6
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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.

Fermented Soymilk Alleviates Lipid Accumulation by Inhibition of SREBP-1 and Activation of NRF-2 in the Hepatocellular Steatosis Model

  • Ahn, Sang Bong;Wu, Wen Hao;Lee, Jong Hun;Jun, Dae Won;Kim, Jihyun;Kim, Riji;Lee, Tae-bok;Jun, Jin Hyun
    • Journal of Microbiology and Biotechnology
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    • v.28 no.2
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    • pp.236-245
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    • 2018
  • Ingredients of soy and fermented soy products have been widely utilized as food supplements for health-enhancing properties. The aim of this study was to evaluate the effects of fermented soymilk (FSM) and soymilk (SM) on free fatty acid-induced lipogenesis in the hepatocellular steatosis model. HepG2 cells were incubated with palmitic acid (PA) for 24 h to induce lipogenesis and accumulation of intracellular lipid contents. The PA-treated cells were co-incubated with FSM, SM, genistein, and estrogen, respectively. Lipid accumulation in the PA-treated HpG2 cells was significantly decreased by co-incubation with FSM. Treatment of HepG2 cells with PA combined with genistein or estrogen significantly increased the expression of SREBP-1. However, FSM co-incubation significantly attenuated SREBP-1 expression in the PA-treated HepG2 cells; in addition, expression of NRF-2 and phosphorylation of ERK were significantly increased in the PA and FSM co-incubated cells. PA-induced ROS production was significantly reduced by FSM and SM. Our results suggested that the bioactive components of FSM could protect hepatocytes against the lipid accumulation and ROS production induced by free fatty acids. These effects may be mediated by the inhibition of SREBP-1 and the activation of NRF-2 via the ERK pathway in HepG2 cells.

Ginseng-plus-Bai-Hu-Tang ameliorates diet-induced obesity, hepatic steatosis, and insulin resistance in mice

  • Lu, Hsu-Feng;Lai, Yu-Heng;Huang, Hsiu-Chen;Lee, I-Jung;Lin, Lie-Chwen;Liu, Hui-Kang;Tien, Hsiao-Hsuan;Huang, Cheng
    • Journal of Ginseng Research
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    • v.44 no.2
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    • pp.238-246
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    • 2020
  • Background: Dietary fat has been suggested to be the cause of various health issues. Obesity, hypertension, cardiovascular disease, diabetes, dyslipidemia, and kidney disease are known to be associated with a high-fat diet (HFD). Obesity and associated conditions, such as type 2 diabetes mellitus and nonalcoholic fatty liver disease (NAFLD), are currently a worldwide health problem. Few prospective pharmaceutical therapies that directly target NAFLD are available at present. A Traditional Chinese Medicine, ginseng-plus-Bai-Hu-Tang (GBHT), is widely used by diabetic patients to control glucose level or thirst. However, whether it has therapeutic effects on fat-induced hepatic steatosis and metabolic syndrome remains unclear. Methods: This study was conducted to examine the therapeutic effect of GBHT on fat-induced obesity, hepatic steatosis, and insulin resistance in mice. Results: GBHT protected mice against HFD-induced body weight gain, hyperlipidemia, and hyperglycemia compared with mice that were not treated. GBHT inhibited the expansion of adipose tissue and adipocyte hypertrophy. No ectopic fat deposition was found in the livers of HFD mice treated with GBHT. In addition, glucose intolerance and insulin sensitivity in HFD mice was also improved by GBHT. Conclusion: GBHT prevents changes in lipid and carbohydrate metabolism in a HFD mouse model. Our findings provide evidence for the traditional use of GBHT as therapy for the management of metabolic syndrome.