• 제목/요약/키워드: sterol regulatory element binding protein 1

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Effects of Compounds from Physalis angulata on Fatty Acid Synthesis and Glucose Metabolism in HepG2 Cells via the AMP-activated Protein Kinase Pathway

  • Hoa, Hoang Thai;Thu, Nguyen Thi;Dong, Nguyen Thuong;Oanh, Tran Thi;Hien, Tran Thi;Ha, Do Thi
    • Natural Product Sciences
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    • 제26권3호
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    • pp.200-206
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    • 2020
  • The ability of the total extract from Physalis angulata; three fractions after partitioning with n-hexane, ethyl acetate (TBE), and water; and four withanolides (compounds 1 - 4) to phosphorylate 5'-adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) in HepG2 cells was evaluated. The TBE fraction (50 ㎍/mL) activated p-ACC and p-AMPK expression most strongly. Compounds 1 - 4 (10 μM) upregulated p-ACC expression at different levels. Compound 4 induced the most significant changes in p-AMPK expression, followed by 1 and 2. Sterol regulatory element-binding proteins (SREBPs) play a functional role in the transcriptional regulation of the lipogenic pathway, including fatty acid synthase (FAS) and ACC. The effects of compounds 2 and 4 (10 μM) on FAS and SREBP-1c expression under high glucose conditions (30 mM) in HepG2 cells were evaluated further. Both dose-dependently inhibited FAS and SREBP-1c expression as well as lipid accumulation (1 - 10 μM) were compared to high-concentration glucose control, which upregulated FAS and SREBP-1c. These results suggest that compounds 2 and 4 upregulate AMPK, suppress FAS and SREBP-1c, and have potential effects on glucose and lipid metabolism.

Anti-obesity Activity of Ethanol Extract from Bitter Melon in Mice Fed High-Fat Diet

  • Yoon, Nal Ae;Park, Juyeong;Jeong, Joo Yeon;Rashidova, Nilufar;Ryu, Jinhyun;Roh, Gu Seob;Kim, Hyun Joon;Cho, Gyeong Jae;Choi, Wan Sung;Lee, Dong Hoon;Kang, Sang Soo
    • 한국발생생물학회지:발생과생식
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    • 제23권2호
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    • pp.129-138
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    • 2019
  • In many cases, obesity is associated with metabolic disorders. Recently, natural compounds that may be beneficial for improving obesity have received increasing attention. Bitter melon has received attention as a diabetes treatment. $NAD^+$-dependent deacetylase (Sirtuin 1, SIRT1) has emerged as a novel therapeutic target for metabolic diseases. In this study, ethanol extract of bitter melon (BME) suppressed adipocyte differentiation and significantly increased the expression of SIRT1 in fully differentiated 3T3-L1 cells. Moreover, it enhanced the activation of AMP-activated protein kinase (AMPK). In high-fat diet (HFD)-fed induced-obesity mice, BME suppressed HFD-induced increases in body weight and white adipose tissue (WAT) weight. BME also increased the expression of SIRT1 and suppressed peroxisome proliferator-activated receptor and sterol regulatory element binding protein 1 expressions of WAT from HFD-fed mice. These findings suggest that BME prevents obesity by activating the SIRT1 and AMPK pathway and that it may be a useful dietary supplement for preventing obesity.

해독사물탕(解毒四物湯)이 LPS 유도 ICR mouse의 산화스트레스 및 고지혈증에 미치는 효과 (The Effects of Haedoksamul-tang on Oxidative Stress and Hyperlipidemia in LPS-induced ICR Mouse)

  • 최규호;정유선;신현철
    • 대한한의학회지
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    • 제37권1호
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    • pp.77-89
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    • 2016
  • Objectives: The present study was conducted to examine whether Haedoksamul-tang (HS), a traditional oriental herbal medicine, have beneficail effects on anti-inflammation and dyslipidemia in lipopolysaccharide (LPS)-induced ICR mouse. Methods: Twenty four 8-week old male ICR mouse were divided into four groups: normal untreated; LPS treatment only; HS 10 mg/kg plus LPS treatment; and HS 30 mg/kg plus LPS treatment. HS was orally administered per day for 2days. Twenty-four hours after LPS injection (10 mg/kg/day, i.p.), all the mice were sacrificed, and serological changes were evaluated. The levels of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), sterol regulatory element-binding transcription protein 1 (SREBP-1) activity and cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor a (TNF-a), monocyte chemotactic protein 1 (MCP-1), acetyl-CoA carboxylase a (ACCa) expression were analyzed in Western blot analysis. Results: HS inhibited oxidative stress in the liver of LPS-induced ICR mice. The LPS-induced ICR mice exhibited the increase of NF-${\kappa}B$ activity and COX-2, iNOS, TNF-a, MCP-1 expressions in the liver, while HS treatment significantly inhibited them. Moreover, The administration of HS significantly decreased the elevated serum triglyceride and down-regulated the levels of SREBP-1, ACCa in the liver of LPS-induced ICR mice. Conclusions: In conclusion, HS could have hepato-protective effects against the oxidative stress-related inflammation and abnormal lipid metabolism.

Carcass traits, fatty acid composition, gene expression, oxidative stability and quality attributes of different muscles in Dorper lambs fed Nigella sativa seeds, Rosmarinus officinalis leaves and their combination

  • Odhaib, Kifah Jumaah;Adeyemi, Kazeem Dauda;Sazili, Awis Qurni
    • Asian-Australasian Journal of Animal Sciences
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    • 제31권8호
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    • pp.1345-1357
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    • 2018
  • Objective: This study examined the influence of dietary supplementation of Nigella sativa seeds, Rosmarinus officinalis leaves and their combination on carcass attributes, fatty acid (FA) composition, gene expression, lipid oxidation and physicochemical properties of longissimus dorsi (LD), semitendinosus (ST), and supraspinatus (SS) muscles in Dorper lambs. Methods: Twenty-four Dorper lambs ($18.68{\pm}0.6kg$, 4 to 5 months old) were randomly assigned to a concentrate mixture containing either, no supplement (control, T1), 1% Rosmarinus officinalis leaves (T2), 1% Nigella sativa seeds (T3), or 1% Rosmarinus officinalis leaves+1% Nigella sativa seeds (T4) on a dry matter basis. The lambs were fed the treatments with urea-treated rice straw for 90 days, slaughtered and the muscles were subjected to a 7 d postmortem chill storage. Results: The T2 lambs had greater (p<0.05) slaughter and cold carcass weights than the control lambs. Dietary supplements did not affect (p>0.05) chill loss, dressing percentage, carcass composition, intramuscular fat and muscle pH in Dorper lambs. Meat from supplemented lambs had lower (p<0.05) cooking and drip losses, shear force, lightness, and lipid oxidation and greater (p<0.05) redness compared with the control meat. The impact of dietary supplements on muscle FA varied with muscle type. Diet had no effect (p>0.05) on the expression of stearoyl-CoA desaturase and lipoprotein lipase genes in LD and ST muscles in Dorper lambs. The T2 and T3 diets up regulated the expression of AMP-activated protein kinase alpha 2 gene in LD and ST muscles and up regulated the expression of sterol regulatory element-binding protein 1 in ST muscle in Dorper lambs. Conclusion: Dietary supplementation of Nigella sativa seeds and Rosmarinus officinalis leaves had beneficial effects on meat quality in Dorper lambs.

올레산 유도 비알코올성 지방간세포에서 자색옥수수 색소 1호 포엽과 속대 추출물의 지질 축적 억제 효과 (Inhibitory Effect of Purple Corn 'Seakso 1' Husk and Cob Extracts on Lipid Accumulation in Oleic Acid- Induced Non-Alcoholic Fatty Liver Disease HepG2 Model)

  • 이기연;김태희;김재은;배선화;박아름;이효영;최성진;박종열;권순배;김희연
    • 한국식품위생안전성학회지
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    • 제35권1호
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    • pp.93-101
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    • 2020
  • 연구의 목적은 oleic acid로 지방생성이 유도된 HepG2 세포에서 자색옥수수 색소 1호 포엽 및 속대 추출물이 간세포 내 지방생성에 미치는 영향을 구명하는 것이다. 자색옥수수 색소 1호 포엽 및 속대 추출물에 의한 HepG2 세포 내 지방 축적의 변화를 확인하기 위하여 배양된 세포에 oleic acid로 지방 축적을 유도하고 추출물에 의한 중성지방생성 억제 효과를 측정하였으며 추출물을 처리하지 않은 대조군과 추출물을 처리한 실험군의 지방합성 및 축적에 관련된 유전자와 단백질 발현량을 RT-PCR과 Western blot을 통하여 측정하였다. Oil Red O와 Nile Red 염색을 통하여 추출물의 처리로 HepG2 세포 내 중성지방 축적이 억제된 것을 확인하였다. RT-PCR에 의하여 mRNA 발현량을 측정한 결과, oleic acid에 의하여 지방 생성이 유도된 대조군에 비하여 모든 추출물 처리군의 SREBP-1c와 SREBP-1a 유전자 발현량이 유의적으로 감소되었다. Western blot을 실시하여 p-AMPK, p-SREBP1, PPARα, FAS 단백질의 발현량을 측정한 결과, 간에서 지질대사에 관여하는 주요 인자인 SREBP1 단백질의 발현은 추출물의 처리 농도에 따라 유의하게 감소하였으며 지방산의 생합성 경로에 관여하는 주요 효소인 FAS의 단백질 발현향은 모든 처리 농도에서 현저하게 감소된 것이 확인되었다. 본 연구결과는 자색옥수수 색소 1호 포엽 및 속대 추출물이 간세포 내에서 중성지방의 축적을 억제시키고 지질 합성에 관련된 유전자 및 단백질의 발현을 억제시킴으로써 간 세포 내 지질 축적을 완화할 수 있는 기능성 소재로의 활용가치가 높다고 판단된다.

Elevated thyroid hormones caused by high concentrate diets participate in hepatic metabolic disorders in dairy cows

  • Chen, Qu;Wu, Chen;Yao, Zhihao;Cai, Liuping;Ni, Yingdong;Mao, Shengyong
    • Animal Bioscience
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    • 제35권8호
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    • pp.1184-1194
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    • 2022
  • Objective: High concentrate diets are widely used to satisfy high-yielding dairy cows; however, long-term feeding of high concentrate diets can cause subacute ruminal acidosis (SARA). The endocrine disturbance is one of the important reasons for metabolic disorders caused by SARA. However, there is no current report about thyroid hormones involved in liver metabolic disorders induced by a high concentrate diet. Methods: In this study, 12 mid-lactating dairy cows were randomly assigned to HC (high concentrate) group (60% concentrate of dry matter, n = 6) and LC (low concentrate) group (40% concentrate of dry matter, n = 6). All cows were slaughtered on the 21st day, and the samples of blood and liver were collected to analyze the blood biochemistry, histological changes, thyroid hormones, and the expression of genes and proteins. Results: Compared with LC group, HC group showed decreased serum triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol, increased hepatic glycogen, and glucose. For glucose metabolism, the gene and protein expression of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 in the liver were significantly up-regulated in HC group. For lipid metabolism, the expression of sterol regulatory element-binding protein 1, long-chain acyl-CoA synthetase 1, and fatty acid synthase in the liver was decreased in HC group, whereas carnitine palmitoyltransferase 1α and peroxisome proliferator activated receptor α were increased. Serum triiodothyronine, thyroxin, free triiodothyronine (FT3), and hepatic FT3 increased in HC group, accompanied by increased expression of thyroid hormone receptor (THR) in the liver. Conclusion: Taken together, thyroid hormones may increase hepatic gluconeogenesis, β-oxidation and reduce fatty acid synthesis through the THR pathway to participate in the metabolic disorders caused by a high concentrate diet.

Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver

  • Wu, J.;Fu, W.;Huang, Y.;Ni, Y.;Zhao, R.
    • Asian-Australasian Journal of Animal Sciences
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    • 제26권8호
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    • pp.1080-1088
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    • 2013
  • Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum $E_2$ concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol $7{\alpha}$-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase ($ACC_{\alpha}$), malic enzyme (ME), stearoyl-CoA (${\Delta}9$) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ${\alpha}$, ${\beta}$($ER{\alpha}$ and ${\beta}$) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of $ER{\alpha}$ protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

Protective effects against alcoholic liver damage: potential of herbal juice (HJ), blend of Zingiber officinale Roscoe and Pueraria lobata Ohwi extracts

  • 정영윤;최유연;양웅모;안광석
    • 대한융합한의학회지
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    • 제5권1호
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    • pp.45-54
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    • 2023
  • Objectives : Alcohol-induced liver disease advances as to reactive oxygen species (ROS) and cellular lipid peroxidation increase. We examined the hepatoprotective effects of Zingiber officinale Roscoe rhizome extract (ZR), Pueraria lobata Ohwi flower extracts (PF), and a newly developed herbal juice (HJ), which was a combination of ZR and PF extracts, against ethanol-induced hepatotoxicity. Methods: The study utilized the human hepatoma cell line HepG2 cells to validate the hepatoprotective effect of HJ (50~200 ㎍/mL) against ethanol (EtOH, 700 mM)-induced liver damage. Results: HJ effectively reduced the protein expression of sterol regulatory element-binding transcription factor 1, adiponectin, and AMP-activated protein kinase in EtOH-induced HepG2 cells. The levels of ROS, total cholesterol, and triglycerides, which are the result of various synthesis and lipogenesis processes induced by EtOH in the liver, were reduced by HJ. Furthermore, the activities of alcohol dehydrogenase and aldehyde dehydrogenase, enzymes linked to alcohol degradation, were more effectively downregulated by HJ treatment compared to treatment with ZR and PF alone, all without causing cytotoxic effects. Conclusions: HJ protects the liver by inhibiting EtOH-induced lipogenesis, lowering ROS generation, and improving alcohol degradation, which is more effective than ZR and PF alone. Further, in vivo experiments can offer additional evidence regarding the effectiveness, safety, and underlying mechanism of action of HJ.

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Probiotics Increase Intramuscular Fat and Improve the Composition of Fatty Acids in Sunit Sheep through the Adenosine 5'-Monophosphate-Activated Protein Kinase (AMPK) Signaling Pathway

  • Yue Zhang;Duo Yao;Huan Huang;Min Zhang;Lina Sun;Lin Su;LiHua Zhao;Yueying Guo;Ye Jin
    • 한국축산식품학회지
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    • 제43권5호
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    • pp.805-825
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    • 2023
  • This experiment aims to investigate the impact of probiotic feed on growth performance, carcass traits, plasma lipid biochemical parameters, intramuscular fat and triglyceride content, fatty acid composition, mRNA expression levels of genes related to lipid metabolism, and the activity of the enzyme in Sunit sheep. In this experiment, 12 of 96 randomly selected Sunit sheep were assigned to receive the basic diet or the basic diet supplemented with probiotics. The results showed that supplementation with probiotics significantly increased the loin eye area, and decreased plasma triglycerides and free fatty acids, increasing the content of intramuscular fat and triglycerides in the muscle and improving the composition of the fatty acids. The inclusion of probiotics in the diet reduced the expression of adenosine 5'-monophosphate-activated protein kinase alpha 2 (AMPKα2) mRNA and carnitine palmitoyltransferase 1B (CPT1B) mRNA, while increasing the expression of acetyl-CoA carboxylase alpha (ACCα) mRNA, sterol regulatory element-binding protein-1c (SREBP-1c) mRNA, fatty acid synthase mRNA, and stearoyl-CoA desaturase 1 mRNA. The results of this study indicate that supplementation with probiotics can regulate fat deposition and improves the composition of fatty acids in Sunit sheep through the signaling pathways AMPK-ACC-CPT1B and AMPK-SREBP-1c. This regulatory mechanism leads to an increase in intramuscular fat content, a restructuring of muscle composition of the fatty acids, and an enhancement of the nutritional value of meat. These findings contribute to a better understanding of the food science of animal resources and provide valuable references for the production of meat of higher nutritional value.

Bioconversion of Citrus unshiu peel extracts with cytolase suppresses adipogenic activity in 3T3-L1 cells

  • Lim, Heejin;Yeo, Eunju;Song, Eunju;Chang, Yun-Hee;Han, Bok-Kyung;Choi, Hyuk-Joon;Hwang, Jinah
    • Nutrition Research and Practice
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    • 제9권6호
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    • pp.599-605
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    • 2015
  • BACKGROUND/OBJECTIVES: Citrus flavonoids have a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated whether bioconversion of Citrus unshiu with cytolase (CU-C) ameliorates the anti-adipogenic effects by modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 cells. MATERIALS/METHODS: Glycoside forms of Citrus unshiu (CU) were converted into aglycoside forms with cytolase treatment. Cell viability of CU and CU-C was measured at various concentrations in 3T3L-1 cells. The anti-adipogenic and lipolytic effects were examined using Oil red O staining and free glycerol assay, respectively. We performed real time-polymerase chain reaction and western immunoblotting assay to detect mRNA and protein expression of adipogenic transcription factors, respectively. RESULTS: Treatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and instead, increased flavanone aglycoside forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with CU or CU-C at a dose of 0.5 mg/ml. Adipocyte differentiation was inhibited in CU-C group, but not in CU group. CU-C markedly suppressed the insulin-induced protein expression of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) as well as the mRNA levels of $CEBP{\alpha}$, $PPAR{\gamma}$, and sterol regulatory element binding protein 1c (SREBP1c). Both CU and CU-C groups significantly increased the adipolytic activity with the higher release of free glycerol than those of control group in differentiated 3T3-L1 adipocytes. CU-C is particularly superior in suppression of adipogenesis, whereas CU-C has similar effect to CU on stimulation of lipolysis. CONCLUSIONS: These results suggest that bioconversion of Citrus unshiu peel extracts with cytolase enhances aglycoside flavonoids and improves the anti-adipogenic metabolism via both inhibition of key adipogenic transcription factors and induction of adipolytic activity.