• Title/Summary/Keyword: Hepatic lipid

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The Immune Landscape in Nonalcoholic Steatohepatitis

  • Sowmya Narayanan;Fionna A. Surette;Young S. Hahn
    • IMMUNE NETWORK
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    • v.16 no.3
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    • pp.147-158
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    • 2016
  • The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

Pinus Densiflora Bark Extract (PineXol) Decreases Adiposity in Mice by Down-Regulation of Hepatic De Novo Lipogenesis and Adipogenesis in White Adipose Tissue

  • Ahn, Hyemyoung;Go, Gwang-woong
    • Journal of Microbiology and Biotechnology
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    • v.27 no.4
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    • pp.660-667
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    • 2017
  • PineXol, extracted from Korean red pine bark, has beneficial effects, such as antioxidant, antiinflammatory, and antilipogenic activities in vitro. We tested the hypothesis that PineXol supplementation could have anti-obesity effects on mice fed a high-fat diet (HFD). Four-week-old male C57BL/6 mice were fed normal chow (18% kcal from fat) or a HFD (60% kcal from fat). HFD-fed animals were also subjected to PineXol treatment at a dose of 10 or 50 mg/kg body weight (BW) (PX10 or PX50, respectively) body weight. The body weight and body fat mass in the PX50 group were statistically lower than those in the HFD group (p < 0.05 and p < 0.001, respectively). The concentration of hepatic triglycerides, total cholesterol, and low-density lipoprotein cholesterol were reduced in the PX50 group compared with the HFD group (p < 0.01). Acetyl CoA carboxylase (p < 0.01), elongase of very long chain fatty acids 6 (p < 0.01), stearoyl CoA desaturase 1 (p < 0.05), microsomal triglyceride transfer protein (p < 0.01), and sterol regulatory element-binding protein 1 (p < 0.05) were significantly decreased in the PX50 group compared with that in the HFD group. In white adipose tissue, CCAAT-enhancer-binding protein alpha (p < 0.05), peroxisome proliferator-activated receptor gamma (p < 0.001), and perilipin (p < 0.01) were decreased in the PX50 group compared with those in the HFD group. Therefore, the current study implies the potential of PineXol for the prevention and/or amelioration of obesity, in part by inhibition of both hepatic lipid synthesis and adipogenesis in white adipose tissue.

Effect of High Dietary Carbohydrate on the Growth Performance and Physiological Responses of Juvenile Wuchang Bream, Megalobrama amblycephala

  • Zhou, C.P.;Ge, X.P.;Liu, B.;Xie, J.;Miao, L.H.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.11
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    • pp.1598-1608
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    • 2013
  • An optimum dietary carbohydrate content is important for maximum fish growth. In this study, we fed Wuchang bream (Megalobrama amblycephala) with either control diet (30.42%) or high carbohydrate diet (52.92%) for 90 d. Fish were fed to apparent satiation three times daily in an aquarium with automatic temperature control and circulated water. Growth performance, plasma biochemical parameters, hepatic morphology and enzyme activities were determined. It was shown that compared to fish fed control diet, fish fed high carbohydrate diet had higher plasma triglyceride and cortisol levels for d 90, and lower alkaline phosphatase level for d 45, lower hepatic superoxide dismutase and total antioxidative capacity for d 90, higher malondialdehyde for d 45 and glycogen content for d 45 and 90 (p<0.05). Histological and transmission electron microscopy studies showed that hepatocytes of fish fed high carbohydrate diet contained large lipid droplets, causing displacement of cellular organelles to periphery of hepatocytes. The relative level of hepatic heat shock protein 70 (HSP70) mRNA of Wuchang bream fed high carbohydrate diet was significantly higher than that of fish fed the control diet for 90 d (p<0.05). These changes led to decreased specific growth rate and increased feed conversion ratio (p<0.05). Upon hypoxia challenge, fish fed high carbohydrate diet had higher cumulative mortality than those fed the control diet (p<0.05). These results suggested that high dietary carbohydrate (52.92%) was detrimental to the growth performance and health of Wuchang bream.

Effect of Thiol-reducing Agents and Antioxidants on Sulfasalazine-induced Hepatic Injury in Normotermic Recirculating Isolated Perfused Rat Liver

  • Heidari, Reza;Esmailie, Neda;Azarpira, Negar;Najibi, Asma;Niknahad, Hossein
    • Toxicological Research
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    • v.32 no.2
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    • pp.133-140
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    • 2016
  • Sulfasalzine is a widely administered drug against inflammatory-based disorders in human. However several cases of liver injury are associated with its administration. There is no stabilized safe protective agent against sulfasalazine-induced liver injury. Current investigation was designed to evaluate if N-acetylcysteine (NAC) and dithioteritol (DTT) as thiol reducing agents and/or vitamins C and E as antioxidants have any protective effects against sulfasalazine-induced hepatic injury in an ex vivo model of isolated rat liver. Rat liver was canulated and perfused via portal vein in a closed recirculating system. Different concentrations of sulfasalazine and/or thiol reductants and antioxidants were administered and markers of organ injury were monitored at different time intervals. It was found that 5 mM of sulfasalazine caused marked liver injury as judged by rise in liver perfusate level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) (p < 0.05). A significant amount of lipid peroxidation and hepatic glutathione depletion were detected in drug-treated livers, accompanied with significant histopathological changes of the organ. Administration of NAC ($500{\mu}M$), DTT (${400\mu}M$), Vitamin C ($200{\mu}M$), or vitamin E ($200{\mu}M$) significantly alleviated sulfasalazine-induced hepatic injury in isolated perfused rat liver. The data obtained from current investigation indicate potential therapeutic properties of thiol reductants and antioxidants against sulfasalazine-induced liver injury.

Acute hepatic injury following ischemia and reperfusion in rats

  • Park, Mee-Jung-;Lee, Sang-Ho-;Park, Doo-Soon-;Cho, Tai-Soon;Lee, Sun-Mee-
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.340-340
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    • 1994
  • Since total hepatic ischemia(IS) occurs with transplantation, there has been interest in evaluating hepatic function after ischemia and subsequent reflow of blood. Four groups of animals were studied: group 1 (sham), group 2 (30mins IS), group 3 (60mins IS), and g.cup 4 (90mins IS). Serum transaminase(STA), wet weight-to-dry weight ratio(W/D), lipid peroxides(LPO), glucose-6-phosphatase(G-6-Pase) activity, Na$\^$+//K$\^$+/-ATPase(ATPase) activity were measured at 1, 5 and 24hrs after hepatic ischemia. Significant changes occurred between 1 and 5hrs of reperfusion. STA was 3579${\pm}$401, 4593${\pm}$675 and 6348${\pm}$808 U/L in group 2, 3 and 4 respectively. These changes were ischemic time-dependent manner. W/D in group 3 and 4 were significantly increased than that in sham group at all time points measured. In sham group, the level of LPO in the liver microsome remained constant at approximately 0. 5nmole MDA formed/mg protein througllout the experiment, In all ischemic groups on the other hand, the level of LPO started to increase at ischemia and markedly increased at all reperfusion period. Similar to STA, these changes were also dependent on duration of ischemia. Although G-6-Pase activity remained unchanged in both group 2 and group 3 until 5hrs of reperfusion, marked decrease in G-6-Pase activity was observed at grcup 4. ATPase activity was significantly decreased at 1, 5 and 24 hrs of reperfusion in group 3, whereas it was not changed in group 2. Furthermore, ATPase activity in group 4 started to decrease at ischemia and markedly decreased for entire reperfusion period. These data suggest that severity of hepatocellular injury is associated with period of ischemia as well as period of reperfusion.

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Effect of Feelch on Blood Alcohol Concentration in Human and Hepatic Alcohol Metabolizing Enzyme Activity in Alcohol-Fed Rats (필치가 혈중 알코올농도와 간세포내 알코올대사 효소 활성에 미치는 영향)

  • Lee O Mi;Ye Choong Min;Choi Byung Chul;Lee Ji Yun;Kang Hye Jeong;Choi Yun Kyoung;Kim Chang Jong;Sim Sang Soo
    • YAKHAK HOEJI
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    • v.49 no.4
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    • pp.340-346
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    • 2005
  • To investigate the effect of Feelch on alcohol metabolism, we measured both blood alcohol concentration in human and hepatic alcohol metabolizing enzyme activity in rats. The blood alcohol concentration in Feelch-ingested group was significantly lower than that in water-ingested group at 0, 40, and 80 minute after alcohol intake. The blood alcohol concentration between male and female taken 300ml of $21\%$ alcohol showed the significant differences; the peak value of blood alcohol concentration in male and female were $0.083\pm0.014\%\;and\;0.108\pm0.018\%$, respectively. In alcohol-fed rats, aldehyde dehydrogenase (ALDH) activity was significantly increased, whereas alcohol dehydrogenase (ADH) activity was not changed. In both Feelch-fed group and Feelch plus alcohol-fed group, ADH and ALDH activity were significantly increased as compared with each control group. Feelch decreased phospholipase $A_2$ activity and lipid peroxidation in hepatic tissue and activities of serum aminotransferases as compared with control. These results suggest that Feelch may have a hepatoprotective effects and this is likely due to lower blood alcohol concentration via the increment of hepatic ADH and ALDH activity.

Antiviral Efficacy of a Short PNA Targeting microRNA-122 Using Galactosylated Cationic Liposome as a Carrier for the Delivery of the PNA-DNA Hybrid to Hepatocytes

  • Kim, Hyoseon;Lee, Kwang Hyun;Kim, Kyung Bo;Park, Yong Serk;Kim, Keun-Sik;Kim, Dong-Eun
    • Bulletin of the Korean Chemical Society
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    • v.34 no.3
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    • pp.735-742
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    • 2013
  • Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.

Alteration of Lipid Metabolism by Ginseng Supplements With Different Levels of Vitamin E in High Cholesterol-Fed Rats

  • Do, Kyung-Min;Park, Yong-Bok;Bok, Song-Hae;Lee, Mi-Kyung;Jeong, Tae-Sook;Choi, Myung-Sook
    • Preventive Nutrition and Food Science
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    • v.6 no.1
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    • pp.66-72
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    • 2001
  • Ginseng may have antioxidant and pharmacologic effects similar to those of vitamin E. The interactive effect of ginseng and vitamin E was studied with respect to cholesterol metabolism and the antioxidant status. A ginseng supplement (0.1%, wt/wt) with comparable levels of vitamin E was provided with a high-cholesterol (1%, wt/wt) diet to rats for 5 weeks. The amount of vitamin E included in the ginseng-free and ginseng diets was either a low (low-E) or a normal (normal-E) level. The ginseng supplements significantly (p<0.05) altered the concentrations of plasma triglycerides in both the low-vitamin E group and normal-vitamin E group compared to the each ginseng-free group. The hepatic triglyceride and cholesterol content were not significantly (p>0.05) different between groups regardless of the vitamin E level in the diet. The hepatic HMG-CoA reductase activity was significantly (p<0.05) lowered by the ginseng supplement in both the low-vitamin E and the normal-vitamin E groups compared to the ginseng-free group. The HMG-CoA reductase activity was also significantly (p<0.05) lowered with in increase of the dietary vitamin E in the ginseng-free group. The excretion of fecal neutral sterol was significantly (p<0.05) lower in the normal-E ginseng group than th low-E ginseng-free group. Neither dietary ginseng nor vitamin E significantly changed the hepatic antioxidant enzymes activity. This data indicates that ginseng supplements lower the concentration of plasma triglyceride and hepatic HMG-CoA reductase activity regardless of eh dietary vitamin E level. This information may contribute to understanding the interactive effect of ginseng and vitamin E on cholesterol biosynthesis in high cholesterol-fed rats.

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