• Molecular & Cellular Toxicology
• /
• 제2권1호
• /
• pp.48-53
• /
• 2006

[ ${\alpha}-Naphthylisothiocyanate$ ] (ANIT) induces intrahepatic cholestasis, involving damage to biliary epitheial cells. This study investigates hepatic gene expression and histopathological alterations in response to ANIT treatment in order to elucidate early time response of ANIT-induced hepatotoxicity. ANIT was treated with single dose (3, 6, and 60 mg/kg) in corn oil by oral gavage. Serum biochemical and histopathological observation were performed for evaluation of hepatotoxicity level. Affymetrix oligo DNA chips were used for gene expression profile by ANIT-induced hetpatoxicity. Hepatic enzyme levels (ALT, AST, and ALP) were increased in 24 hr high dose group. In microscopic observations, moderate hepatocellular necrosis, were confirmed 24 hr high dose groups. We found that gene expression patterns were dependent on time and dose. Our selected genes were related inflammation and immunomodulation. In this study, ANIT-induced hepatotoxicity was involved in acute phase responses and provides evidence for role of neutrophil could be mechanism associated with ANIT-mediated hepatotoxicity.

• 대한의생명과학회지
• /
• 제18권3호
• /
• pp.227-236
• /
• 2012

Previous study showed that swimming improved obesity but was not through $PPAR{\alpha}$ activation in liver and skeletal muscle in high fat diet-fed female mice with functioning ovaries as an animal model of obese premenopausal women. Thus, this study was aimed at investigation of the effects of swimming on the promotion of health and its molecular mechanism in adipose tissue of high fat diet-fed female mice. Eight-week-old female C57BL/6J mice were randomly divided into two groups (a non-swim control group and a swim group, n=8/group). Mice in the swim group swam for 2 h daily for 6 weeks in water bath with temperature of $35{\pm}1^{\circ}C$. All the animals received high fat diet (45% kcal fat) for 6 weeks. Reverse transcription-polymerase chain reaction was used to elucidate the molecular mechanism. Female mice subjected to swimming had significantly decreased body weight gain and white adipose tissue mass compared with the female control mice. Histological studies illustrated that swimming decreases the hepatic lipid accumulation. As expected, swimming did not affect the expression of mRNA levels of peroxisome proliferator-activated receptor (PPAR) ${\alpha}$ and $PPAR{\alpha}$ target genes responsible for mitochondrial fatty acid ${\beta}$-oxidation, such as carnitine palmitoyltransgerase-1 and medium chain acyl-CoA dehydrogenase in the white adipose tissue. However, mice that underwent 6-weeks of swimming exercise had decreased the mRNA expression of lipogenic genes, such as sterol regulatory element-binding proteins-1C and fatty acid synthase in comparison to sedentary control mice, with decreased $PPAR{\gamma}$ target genes involved in adipocyte-specific marker genes, such as adipocyte fatty acid binding protein and leptin in the white adipose tissue. These results suggest that swimming can effectively prevent obesity induced by high fat diet-fed, in part through down-regulation of adipogenesis and lipogenesis in white adipose tissue of female obese mice. Moreover, these results suggest that swimming maybe contributing the promotion of health through regulation of adipogenesis and lipogenesis in overweight premenopausal women.

• Asian-Australasian Journal of Animal Sciences
• /
• 제21권4호
• /
• pp.590-595
• /
• 2008

The aim of our study was to research the effect of overfeeding on plasma parameters and mRNA expression of genes associated with hepatic lipogenesis in the Sichuan white goose and Landes goose. Fifty-four male Landes geese and 57 male Sichuan white geese were hatched on the same day under the same feeding conditions. After overfeeding for 14 days, (1) extrahepatic adipose tissues grew greatly in the Sichuan white geese, while more lipid accumulated in liver tissue in the Landes geese. (2) Sichuan white geese had a higher plasma concentration of triacylglycerols (TG), lipoproteins and insulin than the Landes geese. However, the Landes geese exhibited higher increase of plasma concentrations of TG, lipoproteins and insulin, with greater decrease of the diacylglycerol acyltransferase 2 (DGAT2) activity and DGAT2 mRNA level and a smller decrease of plasma glucose concentration. In addition, the mRNA level of MTP and LPL in liver was down- and up- regulated by overfeeding, respectively. (3) The correlations between the activity of LPL and the proportions of subcutaneous adipose tissue, abdominal adipose tissue, and liver weight, and the plasma concentration of VLDL were different in the two breeds. (4) The proportion of fatty liver weight was positively correlated to plasma concentrations of VLDL and TG in the overfed Sichuan white geese. Such a relationship did not exist in the Landes geese. (5) The activity of DGAT2 and its mRNA abundance in liver had significant negative correlations with the TG content in liver lipid and plasma insulin level in the Landes geese, while in the Sichuan white geese they had negative correlation (p>0.05) with TG concentration in liver lipid and had significant positive correlation with VLDL and TG concentrations in plasma.

• Asian-Australasian Journal of Animal Sciences
• /
• 제28권3호
• /
• pp.374-381
• /
• 2015

This study aimed to evaluate the effects of vitamin E (VE), ferulic acid (FA) and their combination supplementation on meat quality and antioxidant capacities of finishing pigs. Sixty barrows were randomly allocated to four experimental diets using a $2{\times}2$ factorial arrangement with 2 VE supplemental levels (0 or 400 mg/kg) and 2 FA supplemental levels (0 or 100 mg/kg) in basal diets. After 28 days, six pigs per treatment were slaughtered. The results showed that VE supplementation increased loin eye area of pigs (p<0.05) and FA supplementation increased $pH_{45min}$ value (p<0.05). The interaction of $FA{\times}VE$ was observed in shear force of longissimus dorsi muscle (p<0.05). Moreover, supplementation with VE decreased hepatic and sarcous malondialdehyde (MDA) content, increased hepatic glutathione (GSH) content and sarcous glutathione peroxidase (GSH-Px) activity (p<0.05). Additionally, supplementation with FA increased hepatic GSH-Px activity and decreased sarcous MDA content (p<0.05). However, dietary treatment did not affect the expression of genes related to nuclear factor, erythroid 2-like 2 (NFE2L2) pathway. These results suggest that dietary FA and VE could partially improve meat quality and antioxidant capacity of finishing pigs, but not by activating NFE2L2 pathway under the normal conditions of farming.

• Nutrition Research and Practice
• /
• 제15권4호
• /
• pp.431-443
• /
• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• 생약학회지
• /
• 제53권3호
• /
• pp.145-152
• /
• 2022

Type II diabetes mellitus (T2DM) is a chronic metabolic disease caused by insulin resistance, and abnormally elevated hepatic gluconeogenesis is characterized. Phillyrin, one of the major active constituents of Forsythia suspense, is known to possess the anti-inflammatory and anti-oxidant effects. However, the anti-diabetes mellitus effect of phillyrin and its molecular mechanisms are unclear. The aim of the current study was to investigate the role of phillyrin on gluconeogenesis in insulin resistant HepG2 cells. Phillyrin suppressed high glucose (HG)-induced glucose production. In addition, phillyrin reduced HG-induced the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase), major genes in hepatic gluconeogenesis. Phillyrin treatment attenuated HG-induced nucleus protein levels of FOXO1 and HDAC5 and increased the phosphorylation of Akt, AMPK, HDAC5, and FOXO1. The block of AMPK and Akt activity did not exert the inhibitory effect of phillyrin on gluconeogenesis in insulin resistant HepG2. Taken together, these results suggest that phillyrin inhibits gluconeogenesis of hepatocytes to improve glucose metabolism, through the regulation of LKB1/AMPK/HDAC5 and PI3K/AKT/FOXO1 pathway. These results indicate that phillyrin may be useful in improving hepatic gluconeogenesis associated with insulin resistant and T2DM.

• Animal Bioscience
• /
• 제34권7호
• /
• pp.1210-1220
• /
• 2021

Objective: Unlike mammals, goose fatty liver shows a strong tolerance to fatty acids without obvious injury. Stearyl-coenzyme A desaturase 1 (SCD1) serves crucial role in desaturation of saturated fatty acids (SAFs), but its role in the SAFs tolerance of goose hepatocytes has not been reported. This study was conducted to explore the role of SCD1 in regulating palmitic acid (PA) tolerance of goose primary hepatocytes. Methods: 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide was examined to reflect the effect of PA on hepatocytes viability, and quantitative polymerase chain reaction was used to detect the mRNA levels of several genes related to endoplasmic reticulum (ER) stress, inflammation, and apoptosis, and the role of SCD1 in PA tolerance of goose hepatocytes was explored using RNA interfere. Results: Our results indicated that goose hepatocytes exhibited a higher tolerant capacity to PA than human hepatic cell line (LO2 cells). In goose primary hepatocytes, the mRNA levels of fatty acid desaturation-related genes (SCD1 and fatty acid desaturase 2) and fatty acid elongate enzyme-related gene (elongase of very long chain fatty acids 6) were significantly upregulated with 0.6 mM PA treatment. However, in LO2 cells, expression of ER stress-related genes (x box-binding protein, binding immunoglobulin protein, and activating transcription factor 6), inflammatory response-related genes (interleukin-6 [IL-6], interleukin-1β [IL-1β], and interferon-γ) and apoptosis-related genes (bcl-2-associated X protein, b-cell lymphoma 2, Caspase-3, and Caspase-9) was significantly enhanced with 0.6 mM PA treatment. Additionally, small interfering RNA (siRNA) mediated downregulation of SCD1 significantly reduced the PA tolerance of goose primary hepatocytes under the treatment of 0.6 mM PA; meanwhile, the mRNA levels of inflammatory-related genes (IL-6 and IL-1β) and several key genes involved in the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT), forkhead box O1 (FoxO1), mammalian target of rapamycin and AMPK pathways (AKT1, AKT2, FoxO1, and sirtuin 1), as well as the protein expression of cytochrome C and the apoptosis rate were upregulated. Conclusion: In conclusion, our data suggested that SCD1 was involved in enhancing the PA tolerance of goose primary hepatocytes by regulating inflammation- and apoptosis-related genes expression.

• Journal of Ginseng Research
• /
• 제39권3호
• /
• pp.199-205
• /
• 2015

Background: Ginsenoside Rb1 (G-Rb1), the major active constituent of ginseng, improves insulin sensitivity and exerts antidiabetic effects. We tested whether the insulin-sensitizing and antidiabetic effects of G-Rb1 results from a reduction in ectopic fat accumulation, mediated by inhibition of lipolysis in adipocytes. Methods: Obese and diabetic db/db mice were treated with daily doses of 20 mg/kg G-Rb1 for 14 days. Hepatic fat accumulation was evaluated by measuring liver weight and triglyceride content. Levels of blood glucose and serum insulin were used to evaluate insulin sensitivity in db/db mice. Lipolysis in adipocytes was evaluated by measuring plasma-free fatty acids and glycerol release from 3T3-L1 adipocytes treated with G-Rb1. The expression of relevant genes was analyzed by western blotting, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay kit. Results: G-Rb1 increased insulin sensitivity and alleviated hepatic fat accumulation in obese diabetic db/db mice, and these effects were accompanied by reduced liver weight and hepatic triglyceride content. Furthermore, G-Rb1 lowered the levels of free fatty acids in obese mice, which may contribute to a decline in hepatic lipid accumulation. Corresponding to these results, G-Rb1 significantly suppressed lipolysis in 3T3-L1 adipocytes and upregulated the perilipin expression in both 3T3-L1 adipocytes and mouse epididymal fat pads. Moreover, G-Rb1 increased the level of adiponectin and reduced that of tumor necrosis factor-${\alpha}$ in obese mice, and these effects were confirmed in 3T3-L1 adipocytes. Conclusion: G-Rb1 may improve insulin sensitivity in obese and diabetic db/db mice by reducing hepatic fat accumulation and suppressing adipocyte lipolysis; these effects may be mediated via the upregulation of perilipin expression in adipocytes.

• 대한한방내과학회지
• /
• 제31권2호
• /
• pp.314-330
• /
• 2010

Objective : This study was performed to investigate the anti-fibrogenic effect and changes of inflammation-related genes by YBR I and YBR II (YBR I: Arteisiae Capillaris Herba, Atractylodis Rhizoma Alba, Hoelen/ YBR II: YBR I +Sanguisorbae Radix, Biotae Cacumen, Cirsii Japonici Herba) on HSC(hepatic stellate cells)-T6 and TAA-induced rat liver tissue. Materials and Methods : HSC-T6 were treated with various concentrations of distilled-water extract YBR I and YBR II extract for 24, 48 and 72 hours. After the treatment, cell viability, proliferation, procollagen levels and IL-6 levels were measured by using MTT Assay, BrdU Assay, Procollagen Type 1 C-peptide EIA kit, and Murine IL-6 ELISA Development kit. Rat liver fibrosis was induced by intraperitoneal TAA injection of 150mg/kg 3 times a week for 6 weeks. After the treatment, body weight, liver & spleen weights, liver function test, complete blood cell count and change of portal pressure were studied. In addition, gene expressions of ASMA, IL-6, MMP-2, TIMP-1 and TIMP-2, all of which are known to be associated with liver fibrosis, were analyzed by using Real-Time PCR. After YBR I and YBR IItreatment, percentages of collagen in TAA-induced rat liver tissue were measured. Results : The viability and proliferation of the HSC-T6 decreased as the concentration increased. The production of procollagen decreased as the concentration increased. The production of IL-6 was little influenced by YBR I and YBR II. There was no difference in rat body weight between the TAA-only group and the YBR groups. Compared with rat liver weight of TAA-only group, that of the YBR groups increased. In the YBR I group, the serum level of AST elevated by TAA injection significantly decreased and in the YBR I and II group, the serum level of ALP and ALT elevated by TAA injection decreased. In the YBR I group, white blood cell count elevated by TAA injection decreased but platelets increased. In the YBR I group, the portal pressure elevated by TAA injection significantly decreased. Decreases in the gene expression of ASMA and MMP-2 were observed in the YBR I group. The gene expression of IL-6 was little influenced by YBR I and YBR II -treated groups. In the histological finding, TAA injections caused severe fibrosis, but YBR I and YBR II treatment significantly reduced the amounts of hepatic collagens. Conclusions : These results suggest that YBR I and II have inhibitory effects on the hepatic fibrogenesis.

• Journal of Nutrition and Health
• /
• 제55권1호
• /
• pp.36-46
• /
• 2022

Quercetin의 지질대사 개선 효과에 대한 작용기전을 확인하기 위해 C57BL/6J mouse를 사용하여 실험을 수행하였다. 고콜레스테롤혈증을 유도하기 위해 6주간 1% 콜레스테롤과 0.5% cholic acid를 함유하는 고콜레스테롤 식이를 급여하였으며, quercetin은 0.05%와 0.1%의 수준으로 고콜레스테롤 식이에 추가하여 같은 기간 동안 제공하였다. Quercetin은 혈청과 간의 중성지방 및 콜레스테롤 수준을 용량 의존적으로 감소하는 것으로 나타났다. 고콜레스테롤 식이를 섭취한 쥐의 간에서 지방 합성을 촉진하는 SREBP-1c, ACC1 및 FAS 유전자 발현이 quercetin 섭취에 의해 억제되는 것을 확인하였다. Quercetin은 간세포 내에서 에너지 대사를 조절하는 AMPK 활성을 증가시켰다. 이에 반해 암세포 증식을 촉진하고 지방간에서 높게 발현되는 miR-21 발현은 quercetin 섭취에 의해 감소되었다. 본 연구의 결과는 quercetin이 고콜레스테롤 식이 섭취 쥐에서 혈청과 간의 지질 수준을 낮추는 지질대사 개선 효과가 있으며, 이러한 효과의 일부는 간 내 지방합성 유전자 (SREBP-1c, ACC1 및 FAS) 발현, AMPK 활성 및 miR-21 조절을 통해 매개된다는 것을 시사한다.