• Molecules and Cells
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• v.44 no.2
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• pp.116-125
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• 2021

Cardiovascular diseases (CVDs) are the most common cause of death in patients with nonalcoholic fatty liver disease (NAFLD) and dyslipidemia is considered at least partially responsible for the increased CVD risk in NAFLD patients. The aim of the present study is to understand how hepatic de novo lipogenesis influences hepatic cholesterol content as well as its effects on the plasma lipid levels. Hepatic lipogenesis was induced in mice by feeding a fat-free/high-sucrose (FF/HS) diet and the metabolic pathways associated with cholesterol were then analyzed. Both liver triglyceride and cholesterol contents were significantly increased in mice fed an FF/HS diet. Activation of fatty acid synthesis driven by the activation of sterol regulatory element binding protein (SREBP)-1c resulted in the increased liver triglycerides. The augmented cholesterol content in the liver could not be explained by an increased cholesterol synthesis, which was decreased by the FF/HS diet. HMG-CoA reductase protein level was decreased in mice fed an FF/HS diet. We found that the liver retained more cholesterol through a reduced excretion of bile acids, a reduced fecal cholesterol excretion, and an increased cholesterol uptake from plasma lipoproteins. Very low-density lipoproteintriglyceride and -cholesterol secretion were increased in mice fed an FF/HS diet, which led to hypertriglyceridemia and hypercholesterolemia in Ldlr-/- mice, a model that exhibits a more human like lipoprotein profile. These findings suggest that dietary cholesterol intake and cholesterol synthesis rates cannot only explain the hypercholesterolemia associated with NAFLD, and that the control of fatty acid synthesis should be considered for the management of dyslipidemia.

• Korean Journal of Medicinal Crop Science
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• v.17 no.2
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• pp.133-138
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• 2009

Nelumbo nucifera (lotus) is known to be a useful medicinal plant and leaf extract contains several flavonoids and alkaloids. To analyze the effect of Nelumbo nucifera leaves extract (NNL) on the HBsAg production, we treated NNL on HepG2.2.15 cells which contain the hepatitis B viral genome and secrete surface antigen into media. NNL suppressed the production of hepatitis B surface antigen as a dose-dependent manner. To analyze the effect of NNL on HBV DNA replication, PCR analysis was performed. NNL was not affected the HBV DNA replication and HBsAg mRNA expression. To understand the effect of NNL on the production of HBsAg, we carried out the analysis of lipid-metabolizing gene expression using one-step RT-PCR. NNL reduced the gene expression of FASN and SREBP2 and increased the expression of LDLR. Triglyceride content of HepG2.2.15 cells was not decreased by treatment of NNL. This result suggests a possibility that NNL may have an effect for the inhibition of hepatitis B surface antigen by modulation of lipid and cholesterol metabolism.

• Journal of Life Science
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• v.25 no.10
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• pp.1081-1090
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• 2015

Diabetes has been one of major health risks in industrialized countries. Allium hookeri is a wild herb distributed in India and Myanmar. The root of the plant has been used as food and medicine in Southeast Asia. We investigated Allium hookeri extract improves type 2 diabetes mellitus in C57BL/KSJ db/db obese mouse. C57BL/KSJ db/db obese mouse arise out of Type 2 diabetes and we treated Allium hookeri methanol extract 400 mg/kg (AH 400), 800 mg/kg (AH 800), positive control group (thiazolidinedine;TZDs) were administered orally for 8weeks. AH treated group normalized lipid enzyme system (triglyceride, total cholesterol, HDL-cholesterol and LDL-cholesterol) and serum glucose, HbA1c and plasma insulin level. AH treated group recovered β-cell damage by hyperglycemia and fatty liver disease. AH treated group significantly up regulated expression of Peroxisome proliferator-activated receptor gamma (PPAR-γ), pyruvate dehydrogenase kinase4 (PDK4), Sterol regulatory element-binding protein 1c (SREBP 1) and fork head box O1 (FOX 01) proteins in C57BL/KSJ db/db obese mouse liver. And we found that AH treated group decreased hepatic malondialdehyde formation in C57BL/KSJ db/db obese mouse liver. These results indicate that Allium hookeri methanol extract might be a potential anti-diabetic agent and could be useful in the treatment of type 2 diabetes mellitus.

• Korean Journal of Poultry Science
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• v.42 no.3
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• pp.231-238
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• 2015

The present study aimed to investigate the effects of lycopene on hepatic metabolic- and immune-related gene expression in laying hens. A total of 48 25-week-old White Leghorn hens were randomly allocated into four groups consisting of four replicates of three birds: control (basal diet), T1 (basal diet + 10 mg/kg of tomato powder-containing lycopene), T2 (basal diet + 10 mg/kg of micelles of tomato powder-containing lycopene), and T3 (basal diet + 10 mg/kg of purified lycopene). Chickens were fed ad libitum for 5 weeks, and then total RNA was extracted from the livers for quantitative RT-PCR analysis. Peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$) expression was decreased in the liver of chickens after lycopene supplementation (P<0.05). Micellar lycopene supplementation decreased the expression of PPAR${\gamma}$ target genes including fatty acid binding protein 4 (FABP4) and fatty acids synthase (FASN) in the T2 group (P<0.05). Sterol regulatory element-binding protein 2 (SREBP2) and C/EBP-${\alpha}$ were also downregulated in hens fed with micellar lycopene (P<0.05). Glucose transporter 8 (GLUT-8) was upregulated in the T2 and T3 groups (P<0.05). However, the expression of carnitine palmitoyltransferase 1 (CPT-1) was not changed by lycopene supplementation. Pro-inflammatory cytokines such as tumor necrosis factor ${\alpha}$ (TNF-${\alpha}$) and interleukin 6 (IL-6) were downregulated by lycopene supplementation (P<0.05). These data suggest that the type of lycopene supplementation is critical and that micelles of tomato powder-containing lycopene may play an important role in the modulation of lipid metabolism and immunity in chickens.

• Journal of Korean Medicine Rehabilitation
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• v.28 no.2
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• pp.1-20
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• 2018

Objectives This study was conducted to experimentally evaluate the effects of Younggyechulgam-tang-ga Hwanggi(YGT) on obesity in mice induced by high fat diet. Methods The experiment was conducted with 4-week-old male mice divided into 5 groups. They were a normal diet group(Nor), a high fat diet group(Veh), a positive drug control group-orlistat 40 mg/kg(Oris), a 1.08 g/kg group(YGTL), and a 2.16 g/kg group(YGTH), and were tested for five weeks. Changes in antioxidant activity, body weight, organ weight, ROS, AST, ALT, TC, TG, HDL-C, LDL-C and lipid metabolism protein were checked. Results YGTL and YGTH group significantly reduced body weight compared to Veh group. YGTH group significantly reduced visceral fat weights compared to Veh group. In blood biochemistry analysis, ROS, AST, ALT, TC, TG and LDL-C in YGTL and YGTH group were significantly lower than Veh group. HDL-C increased significance in YGTL and YGTH group. In antioxidation protein analysis, Catalase, GPx and HO-1 have increased significantly in YGTL and YGTH group. YGTH group have increased $PPAR-{\alpha}$, p-AMPK compared to Veh group. but decreased FAS. SREBP-1, p-ACC levels in YGTL and YGTH group were decreased compared to Veh group, however CPT-1, UCP-2 levels in YGTL and YGTH group were increased compared to Veh group. Conclusions YGT has anti-obesity effects by regulating lipolysis and antioxidation in a diet-induced obesity model. Additional clinical studies are needed.

• Asian-Australasian Journal of Animal Sciences
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• v.25 no.9
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• pp.1300-1308
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• 2012

The 5'-adenosine monophosphate-activated protein kinase (AMPK) is a key part of a kinase-signaling cascade that acts to maintain energy homeostasis. The objective of this experiment was to investigate the possible effects of fasting and refeeding on the gene expression of hypothalamic AMPK, some appetitive regulating peptides and lipid metabolism related enzymes. Seven-day-old male broiler (Arbor Acres) chicks were allocated into three equal treatments: fed ad libitum (control); fasted for 24 h; fasted for 24 h and then refed for 24 h. Compared with the control, the hypothalamic gene expression of $AMPK{\alpha}2$, $AMPK{\beta}1$, $AMPK{\beta}2$, $AMPK{\gamma}1$, Ste20-related adaptor protein ${\beta}$ ($STRAD{\beta}$), mouse protein $25{\alpha}$ ($MO25{\alpha}$) and agouti-related peptide (AgRP) were increased after fasting for 24 h. No significant difference among treatments was observed in mRNA levels of $AMPK{\alpha}1$, $AMPK{\gamma}2$, LKB1 and neuropeptide Y (NPY). However, the expression of $MO25{\beta}$, pro-opiomelanocortin (POMC), corticotropin-releasing hormone (CRH), ghrelin, fatty acid synthase (FAS), acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$), carnitine palmitoyltransferase 1 (CPT-1) and sterol regulatory element binding protein-1 (SREBP-1) were significantly decreased. The present results indicated that 24 h fasting altered gene expression of AMPK subunits, appetite regulation peptides and lipometabolism related factors in chick's hypothalamus; the hypothalamic FAS signaling pathway might be involved in the AMPK regulated energy homeostasis and/or appetite regulation in poultry.

• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.4
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• pp.279-288
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• 2016

To observe the potential hepatoprotective effects of Gongjin-dan on the acute ethanol (EtOH)-induced liver damages in C57BL/6 mice with its possible action mechanisms. EtOH-mediated acute hepatic damages were induced by oral administration of EtOH total 3 doses. The changes on the body weight, liver weight, albumin, TG, AST, ALP, ALT, hepatic TG contents, hepatic antioxidant defense system, TNF-α, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes - SREBP-1c, SCD1, ACC1, FAS, PPARγ and DGAT2 or genes involved in fatty acid oxidation - PPARα, ACO and CPT1 were observed with final liver histopathological inspections after 15 days of continuous administration of silymarin 200 mg/kg, Gongjin-dan (GJD) 400, 200 and 100 mg/kg. The results were compared with silymarin 200 mg/kg treated mice. Marked decreases of body and liver weights, increases of serum AST, ALT, Albumin and TG levels, hepatic TG contents, TNF-α level, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes or decreases mRNA expressions of genes involved in fatty acid oxidation were observed with histopathological changes related hepatosteatosis increases of immunolabelled hepatocytes, as the results of a binge drinking of EtOH in the present study. Also destroys of hepatic antioxidant defense systems were demonstrated in EtOH control mice as compared with intact vehicle control mice, respectively. The results suggest that oral administration of 400, 200 and 100 mg/kg of GJD favorably protected the liver damages from acute mouse EtOH intoxications.

• Journal of Sasang Constitutional Medicine
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• v.30 no.2
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• pp.8-27
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• 2018

Objective This study investigated the effects of Jeoreongchajeonja-tang in a high-fat diet-induced obesity mouse model. Methods The study examined 9-week-old male mice (C57bl/6J) divided into four groups: the normal(C57bl/6J-Nr), control (high-fat diet only; HFD-CTL), positive-control (high-fat diet with Garcinia cambogia), and experimental (high-fat diet with Jeoreongchajeonja-tang; HFD-JCT) groups. After 7 weeks, the body weight, food efficiency ratio, organ weight, and visceral fat weight of the mice were measured. Blood serum tests, mRNA, liver histopathology, and epididymis adipocytes were also examined. Results Compared with the Control(HFD-CTL) group, the Experimental(HFD-JCT) group given Jeoreongchajeonja-tang showed significant reductions in absolute body weight and food efficiency ratio. The serum alanine aminotransferase, total-cholesterol, triglyceride, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, insulin-like growth factor-1, and leptin levels were significantly lower in the experimental group than in the control group. The serum adiponectin levels were significantly higher in the experimental group than in the control group. Compared with the control group, the experimental group showed significant reductions in absolute abdominal subcutaneous fat, epididymal adipose tissue, kidney adipose tissue, intestine adipose tissue, and liver, kidney and spleen adipose tissue weights. The C/EBP-${\beta}$, leptin, and SREBP1c/ADD1 mRNA expression were significantly lower in the experimental group than in the control group, while the UCP-2 and adiponectin mRNA expression were significantly higher. Compared with the control group, the experimental group showed a significant reduction in the absolute adipocyte area in the liver and epididymal adipose tissue. Conclusion Jeoreongchajeonja-tang has an anti-obesity effect. Additional clinical studies are expected.

• Journal of Korean Medicine Rehabilitation
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• v.26 no.2
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• pp.1-12
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• 2016

Objectives The purpose of this study was to evaluate anti-obesity effect of Galgeuntang (gegentang) and elucidate the effect of it on gene expression related to obesity. Methods The experiments were performed with the use of Diet-Induced Obese mice. They were grouped NC (normal control), HFD (high fat diet control), GGT (Galgeun-tang (gegentang), 700 mg/kg), ORL (Orlistat, 10 mg/kg). GGT was orally administered for 12 weeks. Body weight was measured every week. Real-time PCR was performed to investigate the effect of GGT on gene expression in liver tissue. Results GGT group and ORL group were reduced in body weight compared with HFD. HFD increased $PPAR{\gamma}$, SREBP-1, Leptin, aP2, FATP1, FAS gene expression compared with NC. GGT increased FATP1 gene expression. But GGT reduced $PPAR{\gamma}$ & FAS gene expression in liver tissue of diet-induced obese mice compared with HFD. Conclusions These results suggest that GGT is supposed to have a certain impact on the treatment of obesity. But more study is needed in the future.

• The Journal of Pediatrics of Korean Medicine
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• v.24 no.3
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• pp.92-105
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• 2010

Objectives: The purpose of this study is to investigate the effects of Daecheongryong-tang (DCRT) on the adipogenesis in 3T3-L1 preadipocytes. Methods: 3T3-L1 preadipocytes were differentiated with adipogenic reagents by incubating for 2 days in the absence or presence of DCRT ranging 0.25 and 2%. The effect of DCRT on adipogenesis was examined by Oil red O staining, and the protein, RNA, and RT-PCR were measured. Results: Our results showed that DCRT decreased the TG content by ORO staining. To elucidate the mechanism of the effects of DCRT on lowering TG content in 3T3-L1 adipocytes, we examined the DCRT modulate expressions of transcription factors to induce adipogenesis and adipogenic genes which is related to the regulation of accumulation of lipids. As a result, the expression of SREBP1, C/$EBP{\beta}$, C/$EBP{\delta}$, C/$EBP{\alpha}$, and $PPAR{\gamma}$ genes, which induce the adipose differentiation and adipose-specific aP2, adipsin, LPL, CD36, TGF-${\beta}$ and adiponectin genes which regulates fat formations, were decreased. In addition, DCRT reduced the expression of iNOS and IL-6 in 3T3-L1 adipocytes, resulting in inflammation. Conclusions: DCRT could regulate transcript factor related to induction of adipose differentiation, inhibit the accumulation of lipids and expression of the adipogenic genes.