• Title/Summary/Keyword: HMGCR

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Regulation of the Lactobacillus Strains on HMGCoA Reductase Gene Transcription in Human HepG2 Cells via Nuclear Factor-κB

  • Chen, Kun;Li, Shaocong;Chen, Fang;Li, Jun;Luo, Xuegang
    • Journal of Microbiology and Biotechnology
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    • v.26 no.2
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    • pp.402-407
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    • 2016
  • Lactic acid bacteria have been identified to be effective in reducing cholesterol levels. Most of the mechanistic studies were focused on the bile salt deconjugation ability of bile salt hydrolase in lactic acid bacteria. However, the mechanism by which Lactobacillus decreases cholesterol levels has not been thoroughly studied in intact primate cells. 3-Hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) is the vital enzyme in cholesterol synthesis. To confirm the effect of probiotic Lactobacillus strains on HMGCR level, in the present study, human hepatoma HepG2 cells were treated with Lactobacillus strains, and then the HMGCR level was illustrated by luciferase reporter assay and RT-PCR. The results showed that the level of HMGCR was suppressed after being treated with the live Lactobacillus strains. These works might set a foundation for the following study of the antihyperlipidemic effects of L. acidophilus, and contribute to the development of functional foods or drugs that benefit patients suffering from hyperlipidemia diseases.

The Effects of Dietary Supplementation of Vitamin C and E on the Growth Performance and the Stress Response in Broiler Chickens (육계에서 비타민 C 및 E의 첨가 급여가 성장 능력과 스트레스 반응에 미치는 영향)

  • Sohn, Sea Hwan;Cho, Eun Jung;Jang, In Surk;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.40 no.1
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    • pp.31-40
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    • 2013
  • This study was performed to investigate the investigated effects of dietary supplementation of vitamin C and E on the growth performance and stress response in broiler chickens. Stress response was analyzed by the quantity of telomeric DNA, the rate of DNA damage and the expression levels of heat shock proteins (HSPs) and hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes on tissues and blood. The telomere length and telomere shortening rates were analyzed by quantitative fluorescence in situ hybridization on the nuclei of lymphocytes and tissues. The DNA damage rate of lymphocytes was quantified by the comet assay. The expression levels of HSP70, HSP90s and HMGCR genes were measured by quantitative real-time polymerase chain reaction in lymphocytes. In results, there was no significant difference among treatments in body weight, weight gain, feed intake and mortality. The telomere shortening rate of the lymphocytes was significantly lower in the vitamin E supplemented group than the control group. The DNA damage was also decreased supplemented with vitamin C and E, as compared to the control group. The vitamin E supplemented group had a significant positive effect on the expressions of HMGCR, HSP90-${\alpha}$ and HSP90-${\beta}$ in lymphocytes, but had no significance on HSP70, as compared to the control group. We concluded that the dietary supplementation of vitamin E (100 mg/kg feed) had reduced the individual physiological stress response without stunt growth in broiler chickens.

Lactobacillus plantarum DR7 Reduces Cholesterol via Phosphorylation of AMPK That Down-regulated the mRNA Expression of HMG-CoA Reductase

  • Lew, Lee-Ching;Choi, Sy-Bing;Khoo, Boon-Yin;Sreenivasan, Sasidharan;Ong, Kee-Leong;Liong, Min-Tze
    • Food Science of Animal Resources
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    • v.38 no.2
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    • pp.350-361
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    • 2018
  • Hypercholesterolemia is one of the primary risk factors for cardiovascular diseases. The use of lactobacilli probiotics to reduce blood cholesterol levels have been extensively reported. However, more information is needed to evaluate the possible mechanisms involved and to identify possible targets for further therapeutic development. In this study, strains of lactobacilli were screened based on the ability to assimilate cholesterol, and prevention of cholesterol accumulation in hepatic (HepG2) and intestinal (HT-29) cells. Cell free supernatant (CFS) from Lactobacillus plantarum DR7 showed a higher ability to assimilate cholesterol, reduction in cholesterol accumulation in both HepG2 and HT-29 cells, accompanied by reduced mRNA expression of HMG-CoA reductase (HMGCR) in HepG2 (p<0.05), compared to other lactobacilli. The reduction of HMGCR expression was also diminished in the presence of an AMPK inhibitor (Compound C), suggesting that L. plantarum DR7 exerted its effect via the AMPK pathway, typically via the phosphorylation of AMPK instead of the AMPK mRNA expression in HepG2 (p<0.05). Altogether, our present study illustrated that lactobacilli could exert cholesterol lowering properties along the AMPK pathway, specifically via phosphorylation of AMPK that led to reduced expression of HMGCR.

Development of Lotus Root Bugak with Plasma Lipid Reduction Capacity by Addition of Opuntia ficus-indica var. saboten or Green Tea as a Coloring Agent (백년초 및 녹차 가루 첨가 연근 부각의 지질저하 기능성)

  • Kim, Mijeong;Hong, Sun Hee;Chung, Lana;Choe, Eunok;Song, Yeong-Ok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.333-340
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    • 2014
  • The purpose of this study was to develop functional lotus root bugak with plasma lipid reduction capacity by controlling the color of batter used for bugak preparation. Lotus root, nearly colorless, was selected to observe color effects. Gardeniae fructus (GF), Opuntia ficus-indica var. saboten (OF), and green tea (GT), which are colored yellow, red, and green, respectively, were used as coloring agents. Fermented glutinous rice was prepared naturally during winter season by placing glutinous rice and water (1:2, w/w) together in a crock pot for 7 days. Coloring materials (10%, w/w) were blended with glue made from fermented glutinous rice flour to prepare the batter. Cooked lotus root was then mixed with a 1.1-fold amount of batter (w/w) and dried at room temperature. Lotus root bugak (LRB) is pan-fried with un-roasted sesame oil, which is traditionally used as frying oil in Korea. Low-density lipoprotein receptor knockout ($LDLr^{-/-}$) mice (n=36) were fed an atherogenic diet (AD) containing various types of LRB (10 g%) for 10 weeks. Plasma triglyceride, total cholesterol, and LDL-C concentrations decreased significantly in mice fed LRB prepared with OF batter (OFB) and GT batter (GTB) (P<0.05). Protein expression levels of fatty acid synthase (FAS) and 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMGCR) in the OFB and GTB groups were suppressed compared with the LRB group (P<0.05). In accordance with the results on FAS and HMGCR expression, sterol regulatory element binding protein-I and II (SREBP-I and II), which are responsible for the regulation of FAS and HMGCR gene expression, respectively, were down-regulated compared to the LRB group (P<0.05). In conclusion, the plasma lipid reduction activities of OFB and GTB could be mediated through down-regulation of FAS and HMGCR mRNA expression via suppression of regulatory molecules, SREBP-I and II, in $LDLr^{-/-}$ mice.

Analysis of Stress Response of Domestic Chicken Breeds for the Development of a New Synthetic Parent Stock (국산 종계 개발을 위한 토종 계통들의 스트레스 반응 정도 분석)

  • Sohn, Sea Hwan;Cho, Eun Jung;Park, Ji Ae;Hong, Young Ho;Kim, Chong Dae
    • Korean Journal of Poultry Science
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    • v.42 no.2
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    • pp.157-167
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    • 2015
  • We compared the degrees of stress response of 12 domestic purebred chicken strains that have been bred at National Institute of Animal Science, RDA, Korea since 1980. As a physiological marker of stress response, the expression levels of heat shock protein (HSP)-70, HSP-$90{\alpha}$, HSP-$90{\beta}$, hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes and telomere length were measured by quantitative real-time polymerase chain reaction using the lymphocytes of 1,101 chickens. There was significant difference in HSP-70, HSP-$90{\alpha}$, HMGCR expression and telomere length among the strains. There was also significant difference in HSP-$90{\alpha}$, HSP-$90{\beta}$, and HMGCR expression between male and female chickens. Different age groups of chicken exhibited different expression levels of HSP-70, HSP-$90{\alpha}$ and telomere length. The results of the HSPs expression level suggested that, the strains of R, L and Y were highly resistant to stress, whereas the strains of S, O and W were susceptible to stress. Although the statistical differences in some of HSPs gene expression existed between genders, the HSP expression results varied in different strains that some opposed to the others, and there might be interaction between strains and genders, which conclude that there was no difference in stress response between male and female chickens. Moreover, despite of significant difference in some of HSPs expression level, it was considered that there was no difference in stress response between ages due to the inconsistent trends among HSP markers.

Effect of extraction conditions on radical scavenging and cholesterol metabolism regulating capacity of silkworm larvae

  • Kim, Soo Hyun;Jo, You-Young;Kweon, HaeYong;Lee, Ji Hae
    • International Journal of Industrial Entomology and Biomaterials
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    • v.43 no.2
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    • pp.45-51
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    • 2021
  • High blood cholesterol levels and oxidized cholesterol are risk factors for cardiovascular disease, which displays high annual incidence. Although studies on sericulture products, including pupae, silk protein, and blood lymph, as hypocholesterolemic substances have been reported, insufficient research in this field has been focused on silkworm larvae. Six larval extracts (Low temperature distilled water, LW; hot temperature distilled water, HW; and 30-100% ethanol, E30-E100) were prepared, and their effects on cholesterol metabolism were examined. LW most potently reduced the risk of cholesterol-related disorders. Polyphenols were highly represented in LW, corresponding with its increased antioxidant potency. The cholesterol biosynthesis enzyme, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) was strongly inhibited by LW. Hepatocytes over-expressed LDL receptor (LDLR) after LW stimulation, promoting cholesterol elimination from plasma. LW also increased ATP binding cassette transporter 1 (ABCA1) gene expression, upregulating HDL biogenesis. In conclusion, LW exhibited strong antioxidant activity, suppressed cholesterol biosynthesis, improved LDL uptake from plasma, and upregulated HDL biosynthesis. In aggregate, these activities could reduce blood cholesterol levels and prevent cardiovascular disease.

Effects of Lipopolysaccride-induced Stressor on the Expression of Stress-related Genes in Two Breeds of Chickens (Lipopolysaccride 감염처리가 닭의 품종간 스트레스연관 유전자 발현에 미치는 영향)

  • Jang, In Surk;Sohn, Sea Hwan;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.44 no.1
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    • pp.1-9
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    • 2017
  • The objective of the present study was to determine the expression of genes associated with lipopolysaccharide (LPS)-induced stressor in two breeds of chickens: the Korean native chicken (KNC) and the White Leghorn chicken (WLH). Forty chickens per breed, aged 40 weeks, were randomly allotted to the control (CON, administered the saline vehicle) and LPS-injected stress groups. Samples were collected at 0 and 48 h post-LPS injection, and total RNA was extracted from the chicken livers for RNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In response to LPS, 1,044 and 1,193 genes were upregulated, and 1,000 and 1,072 genes were downregulated in the KNC and WLH, respectively, using a ${\geq}2$-fold cutoff change. A functional network analysis revealed that stress-related genes were downregulated in both KNC and WLH after LPS infection. The results obtained from the qRT-PCR analysis of mRNA expression of heat shock 90 (HSP90), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), activating transcription factor 4 (ATF4), sterol regulatory element-binding protein 1 (SREBP1), and X-box binding protein 1 (XBP1) were confirmed by the results of the microarray analysis. There was a significant difference in the expression of stress-associated genes between the control and LPS-injected KNC and WLH groups. The qRT-PCR analysis revealed that the stress-related $HSP90{\alpha}$ and HMGCR genes were downregulated in both LPS-injected KNC and WLH groups. However, the HSP70 and $HSP90{\beta}$ genes were upregulated only in the LPS-injected KNC group. The results suggest that the mRNA expression of stress-related genes is differentially affected by LPS stimulation, and some of the responses varied with the chicken breed. A better understanding of the LPS-induced infective stressors in chicken using the qRT-PCR and RNA microarray analyses may contribute to improving animal welfare and husbandry practices.

Comparison of Stress Response between Korean Native Chickens and Single Comb White Leghorns subjected to a High Stocking Density (닭의 품종 간 스트레스 반응 정도 비교 분석)

  • Sohn, Sea Hwan;Cho, Eun Jung;Park, Dhan Bee;Jang, In Surk;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.41 no.2
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    • pp.115-125
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    • 2014
  • With Single Comb White Leghorn (WL) and Korean Native Chicken (KNC) breeds, we compared the stress response with chicken breeds that were subjected to a high stocking density. Stress response was analyzed by the quantity of telomeric DNA, the rate of DNA damage and the expression levels of heat shock proteins (HSPs) and hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes on tissues and blood. The telomere length and telomere shortening rates were analyzed by quantitative fluorescence in situ hybridization on the nuclei of lymphocytes and tissues. The DNA damage rate of lymphocytes was quantified by the comet assay. The expression levels of HSP70, HSP90-${\alpha}$, HSP90-${\beta}$ and HMGCR genes were measured by quantitative real-time polymerase chain reaction in lymphocytes. There was no significant difference between KNC and WL in body weight, weight gain, telomere shortening rate and DNA damage rate. However, the growth rate significantly decreased in chickens raised under high stocking density conditions, as compared to the control group. The telomere-shortening rate, DNA damage and HSPs expression of the lymphocytes were significantly higher in the high stocking density group than the control. The stress condition and breeds had a significant effect on the expressions of HSP70, HSP90-${\alpha}$ and HSP90-${\beta}$ in lymphocytes, except HMGCR. The stress response of WL was higher than that of KNC, as analyzed to the expression of HSP70 and HSP90-${\alpha}$. Therefore, we concluded that the chickens which were exposed to a high stocking density had increased the individual physiological stress response regardless of breeds, and White Leghorns are more susceptible to stress condition than Korean Native Chickens.

Acupuncture Effects of Fatty Mice Induced by High Fat Diet (침 자극이 고지방식이로 유발된 비만 백서에 미치는 영향)

  • Woo, Chang-Hoon;Lee, Yong-Eun;Roh, Sung-Soo;Kim, Jae-Soo
    • Journal of Korean Medicine Rehabilitation
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    • v.24 no.3
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    • pp.1-9
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    • 2014
  • Objectives The aim of this study was to investigate the effects of acupuncture on weight loss, food intake, lipid metabolism, adipogenesis. Methods Four week-old C57BL/6J mice acclimatized to the laboratory environment for 1 week were allocated into four groups of 6~8 mice each: normal diet group, high fat diet group, high fat diet group and treated with acupuncture at HT7, high fat diet group and treated with acupuncture at ST36 for 90days. High fat diet group was used to control group. Results 1) Body weight, food intake of the ST36, HT7 groups decreased compared with those of control group. ST36 group was more effective with body weight decrease, and HT7 group was more effective with food intake decrease. 2) NEFA, TG, TC, ALT, AST of the ST36, HT7 groups decreased compared with those of control group. ST36 group was more effective. 3) The expression of SREP-1c, SREBP-2 of the ST36 group decreased compared with those of control group. These decreased rates were statistically significant. SREBP-2 of the HT7 group decreased significantly compared to the control group. 4) LXR, FAS, SCD of the ST36 group decreased significantly compared with control group. 5) p-ACC, HMGCR of the ST36 group decreased significantly compared with those of control group. HMGCR of the HT7 group decreased significantly compared with control group. Conclusions These results suggest that ST36, HT7 acupuncture may be used prevent or treat the obesity induced by high fat diet.

The Effect of Stocking Density on Stress Related Genes and Telomeric Length in Broiler Chickens

  • Beloor, J.;Kang, H.K.;Kim, Y.J.;Subramani, V.K.;Jang, I.S.;Sohn, S.H.;Moon, Yang Soo
    • Asian-Australasian Journal of Animal Sciences
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    • v.23 no.4
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    • pp.437-443
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    • 2010
  • To be economically profitable, the poultry industry demands an increase in stocking density, which could adversely affect chicken welfare. The current study was performed to investigate the effect of stocking density on stress-related, heat shock protein genes (HSP70 and HSP90), 3-hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) gene and telomere length in broiler chickens. Seven-day-old broiler chickens were housed at High (0.0578 $m^2$/bird), Standard (0.077 $m^2$/bird) and Low (0.116 $m^2$/bird) stocking densities with 8 replicates each until 35 d of age. The growth performance, such as body weight gain and average daily feed intake, was found to be significantly (p<0.05) higher in the Low density group, but these parameters did not show any difference between the High and Standard groups. Other growth performance, such as feed conversion ratio and final feed intake, showed no difference among the treated groups. The expression levels of HSP70 and HMGCR were found to be elevated with the increase of stocking density. The expression level of these genes was significantly (p<0.05) higher in the High density stocked group compared with the other groups, whereas the expression levels were not significantly different between the Low and Standard groups. The expression levels of HSP90 did not show any significant changes among the treated groups. The telomeric length of the birds housed in High density was reduced significantly (p<0.05) when compared to that of the birds in Low density. These results clearly indicate that birds stocked at high density show physiological adaptive changes indicative of stress at gene transcriptional and telomere levels.