• Advances in Traditional Medicine
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• v.1 no.1
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• pp.28-36
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• 2000

Effects of hesperetin and naringenin on the concentration of triacylglycerol in the serum and liver were studied in male golden hamster fed with the semipurified diet containing at 1% level of them for 3 weeks. The concentration of triacylglycerol in serum of the naringenin group decreased by 31%, whereas that in liver increased by 37% compared to the control group. The concentration of triacylglycerol in the serum and liver of the hesperetin group was slightly lower than the control group. The activity of microsomal phosphatidate phosphohydrolase in the liver, which is a key enzyme for biosynthesis of triacylglycerol, was significantly inhibited in the hesperetin group, whereas it was not affected in the naringenin group. The effect of hesperetin on phosphatidate phosphohydrolase was also measured in vitro. Hesperetin decreased the activity of phosphatidate phosphohydrolase with a dose-dependent manner. Both naringenin and hesperetin did not statistically affect the daily food consumption, body weight, liver weight, and total cholesterol in the serum. The observation accounts for the hypotriglyceridemic effect of hesperetin in the hyperlipidemic hamster.

• Applied Biological Chemistry
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• v.40 no.6
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• pp.577-582
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• 1997

Effects of four citrus flavonoids, hesperidin, naringin and their aglycones on phosphatidate phosphohydrolase(PAP, EC 3.1.3.3) activity were examined using isolated rat microsomes as an enzyme source. In addition, these flavonoids were tested to see whether they exert any influence on the proliferation and growth in cultured human hepatocytes HepG2 cells. Flavonoids at concentration up to $10{-4}M$ had no significant effect on the number of cells and cell proliferation by MTT cell growth assay method, whereas aglycone flavonoids, hesperetin and narigenin, at concentration of $10{-3}M$ significantly inhibited cell proliferation. Hesperetin inhibited PAP activity in a dose-dependent manner starting at concentration of $10{-5}M$. Narigenin at concentration of $10{-2}M$ inhibited PAP activity markedly, while the other flavonoids did not show any significant effect. The present study, therefore, demonstrated that aglycone flavonoids exerted portent effects on PAP activity and on cell proliferation.

• BMB Reports
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• v.35 no.5
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• pp.494-497
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• 2002

The present study explored the short-term effects of dietary conjugated-linoleic acid (CLA) on liver lipid metabolism in starved/refed Otsuka Long Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (12 weeks old) were starved for 24 hours, then refed for 48 hours with either a CLA diet [7.5% CLA and 7.5% Safflower oil (SAF)] or a SAF control diet (15% SAF). The results demonstrated a 30% reduction of hepatic triglyceride (TG) concentration in the CLA group when compared to the control group. Liver cholesterol concentration was also 26% lower in the CLA fed rats. The activity of mitochondrial carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, was moderately elevated by 1.2-fold in the livers of the CLA group when compared to the control. In contrast, phosphatidate phosphohydrolase, the rate-limiting enzyme for TG synthesis, was found to be 20% lower in the livers of the CLA-fed rats. Therefore, dietary CLA evidently lowers liver lipid concentrations through a reduced TG synthesis and enhanced fatty acid oxidation in starved/refed OLETF rats.

• Journal of the Korean Chemical Society
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• v.42 no.4
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• pp.16-471
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• 1998

• Journal of Life Science
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• v.15 no.4 s.71
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• pp.613-618
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• 2005

We investigated the effect of chicory (Chicorium intybus) extract on triglyceride concentration and microsomal triglyceride transfer protein (MTP) activity in rats. The effect of water-soluble extract of chicory fed at the $2.0\%\;and\;4.0\%(w/w)$ levels for 2 weeks on the concentration of serum triglyceride and the activity of hepatic microsomal riglyceride transfer protein (MTP) was investigated in male Sprague-Dawley rats. The triglyceride concentrations in serum of the chicory extract fed groups were significantly lower than in the control group. MTP activity, known to be essential for the assembly/secretion of apolipoprotein B-containing lipoproteins, was also significantly lower in the chicory extract groups than in the control group. The concentrations of other lipids in serum and liver and the activity of phosphatidate phosphohydrolase, the rate-limiting enzyme in triglyceride synthesis, showed no significant differences among in the chicory fed groups. These results indicate that dietary chicory extract decrease hepatic MTP activity and serum triglyceride concentration, and therefore reduces hepatic lipoprotein assembly and secretion.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.3
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• pp.518-524
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• 2000

치커리 물추출물은 실험동물의 지질대사에 영향을 미치는 것으로 알려져 있으나, 이러한 영향에 대한 대사가 작은 명확하게 밝혀져 있지 않다. \ulcorner음처리한 치커리(roasted-chicory)또는 볶음처리하지 않은 치커리(unroasted-chicory)로부터 물추출한 치커리 추출물을 5% 수준으로 식이에 첨가하여 SD계 수컷흰쥐에 2주간 자유 섭취시켜 혈청 및 간장의 지질 농도와 간장 MTP(microsomai triglyceride trasfer protein) 활성에 미치는 영향을 조사하였다. 체중 증가량, 장기 중량 및 식이 섭취량은 각군잔의 유의적 차이는 인정되지 않았다. 혈당치는 대조군과 볶음처리한 치커리군에 비교해서 볶음처리하지 않은 치커리군에서 증가하는 경향을 나타내었다. 혈청의 TG 농도는 치커리 첨가군에서 감소하는 경향으로 나타났으며, 혈청 총 콜레스테롤, 인지질 및 유리지방산 농도와 간장 지질농도는 실험군간의 유의적 치이는 없었으나, HDL콜레스테롤 농도는 치커리 첨가군에서 증가하는 경향을 보였다. 간장에서 중성 지질 합성의 조절효소로 알려진 PAP(phosphatidate phosphohydrolase)활성은 각 실험 군간의 유의적 치이는 없었다. 그러나, 중성지질-rich 리포단백질의 합성, 분비에 필수적인 간장 MTP활성을 대조군에 비교하여 치커리군에서 현저하게 저해되었다. 간장 MTP 활성과 혈청 중성지질 농도의 사이에 높은 정의 상관관계(r=0.81)가 인정되어, 본 실험에서 치커리 뿌리 추출물에 의한 혈청 중성지질 억제효과는 간장 MTP 활성의 저해에 기인하는 것으로 시사되었다.

• Applied Biological Chemistry
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• v.41 no.6
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• pp.414-420
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• 1998

We studied the difference effects of dietary ${\alpha}-linolenic\;acid\;({\alpha}-LA,\;18:3\;n-3)$, eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) on the lowering of triacylglycerol in the liver and serum on lipid metabolism in rats. Rats were fed semipurified diets containing 10% fat with constant polyunsaturated/monounsaturated/saturated fatty acids (1:1:1) and n-6/n-3 ratio (1:2). EPA (98%) and DHA (98%) were added in diets as the ethyl esters. The concentration of liver triacylglycerol was significantly lower in rats fed both EPA and DHA than in those fed ${\alpha}-LA$. The concentration of liver phospholipid was significantly higher in rats fed DHA than in those fed ${\alpha}-LA$ and EPA. Both EPA and DHA reduced serum triacylglycerol concentration compared with ${\alpha}-LA$, but this effect was more pronounced in the EPA diet. The activity of phophatidate phosphohydrolase in the liver microsome was significantly lower in rats fed both EPA and DHA than in those fed ${\alpha}-LA$. but, there was no significant difference on the activities of diacylglycerol acyltransferase among the three groups. The concentration of liver triacylglycerol were correlated with changes in the microsomal phosphatidate phosphohydrolase activity (r=0.84). Hepatic NADPH generating enzyme, glucose-6-phosphate dehydrogenase was more effective to reduce the activity in rats fed both EPA and DHA than in those fed ${\alpha}-LA$. In conclusion, EPA or DHA reduced the hepatic triacylglycerol concentration by inhibiting microsomal phosphatidate phosphohydrolase, thereby inhibiting synthesis of triacylglycerol in the liver.

• Applied Biological Chemistry
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• v.44 no.2
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• pp.122-128
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• 2001

This review showed a discussion on the biofunctional activities of citrus flavonoids. The major flavonoids of citrus species, hesperidin, hesperetin, naringin, and naringenin, were selected to evaluate their biological effects on the lipid metabolism in rats and hamsters, the proliferation of human hepatocyte HepG2 cells, and the antioxidative effect in lipid peroxidation models. These flavonoids showed hypotriglyceridemic effect in hamsters and hypochloesterolemic effect in rats. They also significantly inhibited the activities of phosphatidate phophohydrolase and acyl-CoA: cholesterol acyltransferase, which are key enzymes for biosynthesis of triglyceride and cholesterol, repectively, in vivo and in vitro experiments. These biofunctional activities by citrus flavonoids were shown more potent in the aglycone flavonoids, hespreretin and naringenin, than their corresponding glycoside flavonoids, hesperidin and naringin. These aglycone flavonoids also have inhibitory effects on proliferation of human hepatocyte cancer HepG2 cells. Hesperidin showed lowering activities of cellular triglyceride and cholesterol concentrations in HepG2 cells. Citrus flavonoids have significant importance in functional food industry as biofunctional active ingredients.

• Korean Journal of Food Science and Technology
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• v.33 no.4
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• pp.492-496
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• 2001

Microsomal triglyceride transfer protein(MTP) activity and mRNA level were investigated in the liver and small intestine of rats fed on di-(2-ethylhexyl)phthalate(DEHP) and orotic acid(OA) as serum triglyceride-reducing agents. The concentration of liver triglyceride was significantly increased in the OA group, but that was not increased in the DEHP group compared with the control group. The concentration of serum triglyceride was significantly decreased in the OA and DEHP groups compared with the control group, but this reduction was more pronounced in the OA group. MTP activity and mRNA level in liver were decreased in the OA group compared with the control group, while MTP activity in the small intestine was increased in the OA group compared with the control group. MTP activities and MTP mRNA levels in both liver and small intestine had no influence by the DEHP dietary feeding, despite the triglyceride-lowering action, compared with the control dietary feeding. The activity of liver microsomal phosphatidate phosphohydrolase(PAP), the rate-limiting enzyme in triglyceride synthesis, was increased in the OA group compared with the control group, but that of cytosolic PAP was decreased in the DEHP group compared with the control group. The result suggest that MTP activity and MTP mRNA level are involved in the triglyceride-lowering action of OA, but those are not involved in that of DEHP.

• Journal of the East Asian Society of Dietary Life
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• v.20 no.1
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• pp.20-29
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• 2010

Naringin has antioxidant and antihyperlipidemic properties, however, phenolic compounds including naringin are unstable in the presence of light, heat and oxygen. Beta-cyclodextrin ($\beta$-CD) is a cyclic heptamer composed of seven glucose units that enhances the stability and solubility of molecules through the formation of inclusion complexes. This study was conducted out to compare the effects of CD-naringin (CD-N) inclusion complexes with naringin on lipid metabolism in high fat-fed animals. Male C57BL/6 mice were fed either CD-N (0.048%, w/w) or naringin (N, 0.02%, w/w) in a 20% high-fat (HFC, 15% lard, 5% corn oil, w/w) diet for 10 weeks. Orlistat (Xenical, 0.01%, w/w) was used as a positive control (PC). There were no differences in body weight, food intake, liver and heart weights, plasma triglyceride(TG), leptin, adiponectin, resistin, IL-$1{\beta}$ and IL-6 concentrations, and hepatic $\beta$-oxidation, carnitine palmitoyl transferase(CPT), glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme activities between the HFC and CD-N groups or between the HFC and N groups. However, both CD-naringin and naringin supplementation les to a significant reduction in the epididymal and perirenal white adipose tissue weights, plasma free fatty acid, insulin and blood glucose concentrations, hepatic cholesterol and TG contents and hepatic fatty acid synthase (FAS), phosphatidate phosphohydrolase (PAP) and HMG-CoA reductase activities compared to the HFC group. The plasma HDL-cholesterol concentration was significantly higher in CD-N and N groups than in HF and PC groups. These results indicate that both CD-naringin and naringin supplementation effectively improved plasma and hepatic lipid metabolism without differences between CD-N and naringin groups.