• Biomolecules & Therapeutics
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• v.25 no.2
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• pp.112-121
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• 2017

Drug-induced liver injury (DILI) is the serious and fatal drug-associated adverse effect, but its incidence is very low and individual variation in severity is substantial. Acetaminophen (APAP)-induced liver injury accounts for >50% of reported DILI cases but little is known for the cause of individual variations in the severity. Intrinsic genetic variation is considered a key element but the identity of the genes was not well-established. Here, pre-biopsy method and microarray technique was applied to uncover the key genes for APAP-induced liver injury in mice, and a cause and effect experiment employing quantitative real-time PCR was conducted to confirm the correlation between the uncovered genes and APAP-induced hepatotoxicity. We identified the innately and differentially expressed genes of mice susceptible to APAP-induced hepatotoxicity in the pre-biopsied liver tissue before APAP treatment through microarray analysis of the global gene expression profiles (Affymetrix $GeneChip^{(R)}$ Mouse Gene 1.0 ST for 28,853 genes). Expression of 16 genes including Gdap10, Lpl, Gabra3 and Ccrn4l were significantly different (t-test: FDR <10%) more than 1.5 fold in the susceptible animals than resistant. To confirm the association with the susceptibility to APAP-induced hepatotoxicity, another set of animals were measured for the expression level of selected 4 genes (higher two and lower two genes) in the liver pre-biopsy and their sensitivity to APAP-induced hepatotoxicity was evaluated by post hoc. Notably, the expressions of Gabra3 and Lpl were significantly correlated with the severity of liver injury (p<0.05) demonstrating that these genes may be linked to the susceptibility to APAP-induced hepatotoxicity.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.9
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• pp.1338-1344
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• 2016

The present study was carried out to evaluate the anti-obesity effect of different concentrations of extracts of hot air-dried ramie leaf (HR) and freeze-dried ramie leaf (FR) in 3T3-L1 cells and pig preadipocytes. To analyze the effect on cell proliferation, cells were treated with $25{\mu}g/mL$ or $100{\mu}g/mL$ HR or FR extract for 2 days. Cell differentiation was evaluated by measuring glycerol-3-phosphate dehydrogenase and lipoprotein lipase (LPL) activities and intracellular triglyceride content. Treatment with either HR or FR extracts inhibited the proliferation of 3T3-L1 cells and pig preadipocytes in a dose-dependent manner. HR extract treatment inhibited the differentiation of both cell types more effectively than FR treatment. The extent of triglyceride accumulation decreased significantly in both cells following either HR or FR treatment. Furthermore, LPL activity significantly decreased after treatment with HR or FR extract. These results indicated that HR and FR extracts may inhibit proliferation and differentiation of 3T3-L1 cells and pig preadipocytes. Further studies are needed to explore the anti-obesity effect of HR and FR extracts.

• Journal of Nutrition and Health
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• v.34 no.4
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• pp.367-374
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• 2001

Conjugated linoleic acid(CLA) is a naturally occuring group of derivatives of linoleic acid found in beef and dairy products. CLA has reported to reduce body fat. This study was designed to observe the effect of CLA supplementation on fat accumulation and degradation in male Sprague Dawley rats. Seventy two rats, weighing 150-180g, were divided into 2 groups according to the types of dietary fat(beef tallow or fish oil) and then each group was divided into 2 groups depending on CLA supplementation, i.e., BT, BT-CLA, FO, FO-CLA. All rats were fed experimental diet containing total fat at 12%(w/w) including CLA at 1% for 30 weeks. At 30 weeks, rats were sacrificed to measure TG, free fatty acid level in plasma, TG, lipogenic enzymes in lever and fat cell size, LPL and HSL activities in epididymal fat fad. Fish oil supplemented with CLA diet showed significant reduction in the food efficiency and weight in 30 weeks-fed rats. CLA supplement did not effect on plasma TG, hepatic TG levels and lipogenic enzymes activities in rats, but, fish oil significantly reduced, The LPL and HSL activities did not affected by CLA supplement and n-3 fatty acid rich fish oil. In conclusion, the results suggest that CLA supplement was not a proper way to reduce the fat accumulation in Sprague Dawley rats. Fish oil supplemented with CLA might better way to reduce the body fatness than fish oil itself. Therefore, It is recommended that further study be performed related to physiological and biochemical effects of CLA supplementation and n-3 fatty acid in rats for the reduction of body fatness.(Korean J Nutrition 34(4) : 367∼374, 2001)

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.9
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• pp.1342-1348
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• 2014

Seeds of Korean pine cone (Pinus koraiensis) have long been consumed as an edible food in countries located in North-East Asia, On the other hand, Korean pine cone, containing various polyphenols, is discarded as a useless garbage after removing seeds. This study investigated the lipolytic effects of pine cone extract in differentiated 3T3-L1 adipocytes. Intracellular lipid accumulation was measured by Oil red O staining, free glycerol release by colorimetric reaction, and expression of genes related to lipid metabolism by real-time PCR. Compared to control, pine cone extract reduced intracellular lipid accumulation by 8.8% and increased free glycerol release by 8.2% a concentration of $5{\mu}g/mL$ in differentiated 3T3-L1 adipocytes. mRNA levels of fatty acid synthesis were not significantly different between control and pine cone extract, but mRNA levels of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) significantly increased by 38.7% and 94.1% at a concentration of $5{\mu}g/mL$, respectively. Thus, pine cone extract is suggested to have lipolytic effects through induction of LPL and HSL gene expression.

• Korean Journal of Medicinal Crop Science
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• v.23 no.3
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• pp.245-252
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• 2015

This study was carried out to investigate the effects of Salvia plebeia R. Br. ethanolic extract with different aspects (stem/leaf and whole plant) on differentiation and lipid accumulation in 3T3-L1 preadipocytes. The morphological changes and the degrees of lipid accumulation in 3T3-L1 cells were measured by Oil Red O staining and intra-cellular triglyceride (TG) assay. The mRNA expressions of special peroxisome proliferation activated receptor- genes (PPAR), CCAAT/ enhancer-binding protein (C/$EBP{\alpha}$), fatty acid synthase (FAS) and lipoprotein lipase (LPL) were detected by reverse transcriptase polymerase chain reaction (RT-PCR). The 50% ethanolic extracts ($100{\mu}g/mL$) of stem and leaf (SALE) and 30% ethanolic extracts (100 g/mL) of whole plant (SAE) from Salvia plebeia R. Br. were significantly attenuated lipid accumulation during adipogenesis in 3T3-L1 cells. Ethyl acetate-soluble fractions ($50{\mu}g/mL$) significantly inhibited lipid droplet accumulation in 3T3-L1 cells. In addition, SALE induced down-regulation of specific adipogenic transcriptional factors (C/$EBP{\alpha}$ and $PPAR{\gamma}$) and target genes (FAS and LPL) during adipogenesis. Salvia plebeia R. Br. may be used as a safe and efficient natural substance to manage obesity.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.10
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• pp.1443-1450
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• 2016

The objective of the current study was to investigate the effects of dietary ${\omega}-6/{\omega}-3$ polyunsaturated fatty acid (PUFA) ratios on lipid metabolism in goslings. One hundred and sixty 21-day-old Yangzhou geese of similar weight were randomly divided into 4 groups. They were fed different PUFA-supplemented diets (the 4 diets had ${\omega}-6/{\omega}-3$ PUFA ratios of 12:1, 9:1, 6:1, or 3:1). The geese were slaughtered and samples of liver and muscle were collected at day 70. The activities and the gene expression of enzymes involved in lipid metabolism were measured. The results show that the activities of acetyl coenzyme A carboxylase (ACC), malic enzyme (ME), and fatty acid synthase (FAS) were lower (p<0.05), but the activities of hepatic lipase (HL) and lipoprotein lipase (LPL) were higher (p<0.05), in the liver and the muscle from the 3:1 and 6:1 groups compared with those in the 9:1 and 12:1 groups. Expression of the genes for FAS (p<0.01), ME (p<0.01) and ACC (p<0.05) were higher in the muscle of groups fed diets with higher ${\omega}-6/{\omega}-3$ PUFA ratios. Additionally, in situ hybridization tests showed that the expression intensities of the high density lipoprotein (HDL-R) gene in the 12:1 and 9:1 groups were significantly lower (p<0.01) than that of the 3:1 group in the muscle of goslings. In conclusion, diets containing lower ${\omega}-6/{\omega}-3$ PUFA ratios (3:1 or 6:1) could decrease fat deposition by inhibiting fat synthesis in goslings.

• Journal of the Korean Society of Food Science and Nutrition
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• v.35 no.4
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• pp.402-409
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• 2006

This study was performed to investigate the effects of Capsosiphon fulvescens (CF) extract on serum and liver lipid metabolism in rats. Male Sprague-Dawley rats were administered 1% cholesterol and 0.25% sodium cholate to induce hypercholesterolemia and were divided into six groups. Experimental groups were administered with following diets; normal diet group (NC), high cholesterol diet group (HC), normal diet and CF extract (200 mg/kg) administered group (NC-CFL), normal diet and CF extract (400 mg/kg) administered group (NC-CFH), high cholesterol diet and CF extract (200 mg/kg) adwlinistered group (HC-CFL), and high cholesterol diet and CF extract (400 mg/kg) administered group (HC-CFH). The body weight gain and feed efficiency ratio were increased by high cholesterol diet, but gradually decreased to the corresponding level of the normal diet group by administered CF extract. The serum total cholesterol concentration of normal diet group was significantly higher than those of NC-CFL group and NC-CFH group. The concentrations of serum total cholesterol LDL-cholesterol and triglyceride and the atherogenic index .were tended to decrease in the CF extract administered groups compared with the high cholesterol diet group. However, HDL-cholesterol and phospholipid concentrations in serum decreased in the high cholesterol diet group and markedly increased by the CF extract administered groups. There were no differences in the concentrations of serum triglyceride, phopholipid, LDL-cholesterol, HDL-cholesterol and free cholesterol in normal diet groups. Concentrations of total cholesterol and triglyceride in liver and kidney were also markedly decreased in the CF administered groups. Total cholesterol and triglyceride concentrations of adipose tissue in the CF administered groups were also decreased compared with the high cholesterol diet group. In addition, there were no differences in the concentrations of liver, kidney and adipose tissue total lipid, triglyceride and total cholesterol in normal diet groups. The activities of heparin-releasable lipoprotein lipase (LPL) and total-extractable LPL in adipose tissue were increased in the high cholesterol diet group compared with the CF extract administered groups, but those of the NC -CFL group and NC-CFH group were similar to the normal diet group. Taken together, it is suggested that the extract of CF have an antiatherosclerotic effect by reducing cholesterol level of serum and liver. Furthermore, the extract of CF decreased LPL activity and triglyceride concentration, resulting in less lipid storage.

• Microbiology and Biotechnology Letters
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• v.45 no.1
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• pp.27-34
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• 2017

$C/EBP{\beta}$ and $C/EBP{\delta}$ are required for the initiation of adipogenesis and induce the expression of key adipogenic regulators, such as $PPAR{\gamma}$ and $C/EBP{\alpha}$. In the present study, we have examined the effects of silibinin and its possible molecular mechanisms in regulating adipocyte differentiation and expression of $C/EBP{\beta}$ and $C/EBP{\delta}$ in the early stage of adipogenesis. Silibinin statistically significantly inhibits intracellular lipid accumulation and the mRNA expression of various genes involved at different stages during adipogenesis. Silibinin also suppresses expression of lipoprotein lipase (LPL), fatty acid binding protein 4 (AP2), and adiponectin in 3T3-L1 adipocytes. Thus, the anti-adipogenic effect of silibinin seems to originate from the ability to inhibit the expression of $C/EBP{\beta}$ and $C/EBP{\delta}$. Furthermore, silibinin decreases cell viability for differentiation period and induces apoptotic cell death through capspase-3 activation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.29 no.3
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• pp.466-470
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• 2000

The current study was undertaken to determine the prolinged effects of fasting-refecding on the lipoprotein lipase (LPL) activity and lipogenesis of adipose tissus in male Sprague-Dawley rals and to investigate the effects of various degrecs of food restriction during refeeding on the LPL activity and lipogenesis. The control group (n=5) was fed ad libitum and killed in the fed state at the beginning of the experiment. All rats except conteol group were fasted for 2 days (n=50). Five rats were killed at the end of fasting and others (n=45) were refed either ad libitum (ad libitum group) or mildly restricted (20% food restricted group), or esverely restricted diet (40% food restricted group). Rats were killed on the day of 7th, 14th, and 21st of refeeding. Lipogenesis was determined by the amount of glucose converted to the total lipid. Body weight and epididymal adipose tissue weight returned to control states by 5 days in ad libitym group and by 14 days in 20% food restricted group. As expected, in 40% food restriction during refeeding weight and epididymal adipose tissue weight did not rcturn to control states until day 21. On day 21 after refeeding, the serum total cholesterol concentration of ad libitum group was significantly (p<0.05) higher than that of control group. The serum HDL-C concentration of 40% food restricted group during refeeding was significantly (p<0.05) higher than that of control group. However, there were no significant dif-ferences in serum HDL-C/total cholesterol (TC) ratio and trigluceride concentration among the groups. Fasting for 2 days decreased lipogenesis and LPL activity (p<0.05). On day 21 after refecding, the lipogencsis of ad libitum group was significantly (p<0.05) lower than that of control group. The lipogenesis of 40% food restricted group during refeeding was significantly (p<0.05) higher than that of conrtol group. Ad libitum group and 20% food restricted group during refecding allowed heparin-releasable (HR) LPL or total extractable (TE) LPL activity to return to control states. 40% food restricted group during refeeding delayed the return of HR-LOL or TE-LPL activity to return to control states until day 21 of refeeding. These results suggest that food restriction during refeeding can partially or completely prevent the overshoot of LPL activity, and this may influence the rate of lipid accumulation in adipose tissue during refeeding.

• Nutritional Sciences
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• v.6 no.3
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• pp.148-154
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• 2003

Although various raw plant materials have been demonstrated to exert anti-obesity effects to a greater or lesser extent in both humans and animals when they are used to supplement the diet, it has not been shown extensively that they influence adipocyte cell differentiation involving lipid metabolic gene expressions. Using a well-established 3T3-L1 preadipocyte differentiation system, we decided to look into molecular and cellular event occurring during adipocyte differentiation when raw plant materials aye included in the process, in an effort to demonstrate the potential use of a screening system to define the functions of traditionally well-known materials. To these ends, the effects of ethanol (EtOH) or EtOH/distilled water (DW) extracts of Wax Gourd were examined using cytochemical and molecular analyses to determine whether components of the extracts modulate adipocyte differentiation of 3T3-Ll preadipocytes in vitro. The cytochemical results demonstrated that EtOH or EtOH/DW extracts did not affect lipid accumulation and cell proliferation, although the degree of lipid accumulation was influenced slightly depending on the extract. EtOH extract was highly effective in apoptotic induction during differentiation of 3T3-Ll preadipocytes (p<0.05). Reverse transcription-polymerase chain reaction (RT-PCR) analysis of lipoprotein lipase (LPL), Uncoupling protein (Ucp) 2, 3 and 4 also showed that while LPL expression was not influenced, Ucp2, 3 and 4 were up regulated in the EtOH extract-treated group and down regulated in the EtOH/DW extract-treated group. These changes in gene expressions suggest that the components in different fractions of Wax Gourd extracts may modulate lipid metabolism by either direct or indirect action. Taking these results together, it was concluded that molecular and cellular analyses of adipocyte differentiation involving lipid metabolic genes should facilitate understanding of cellular events occurring during adipocyte differentiation. Furthermore, the experimental scheme and analytical methods used in this study should provide a screening system for the functional study of raw plant materials in obesity research.