• Journal of Ginseng Research
• /
• 제39권2호
• /
• pp.105-115
• /
• 2015

Background: Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. Methods: The effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. Results: Blood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-a expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. Conclusion: These results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권3호
• /
• pp.161-169
• /
• 2019

Fumigaclavine C (FC), an active indole alkaloid, is obtained from endophytic Aspergillus terreus (strain No. FC118) by the root of Rhizophora stylosa (Rhizophoraceae). This study is designed to evaluate whether FC has anti-adipogenic effects in 3T3-L1 adipocytes and whether it ameliorates lipid accumulation in high-fat diet (HFD)-induced obese mice. FC notably increased the levels of glycerol in the culture supernatants and markedly reduced lipid accumulation in 3T3-L1 adipocytes. FC differentially inhibited the expressions of adipogenesis-related genes, including the peroxisome proliferator-activated receptor proteins, CCAAT/enhancer-binding proteins, and sterol regulatory element-binding proteins. FC markedly reduced the expressions of lipid synthesis-related genes, such as the fatty acid binding protein, lipoprotein lipase, and fatty acid synthase. Furthermore, FC significantly increased the expressions of lipolysis-related genes, such as the hormone-sensitive lipase, Aquaporin-7, and adipose triglyceride lipase. In HFD-induced obese mice, intraperitoneal injections of FC decreased both the body weight and visceral adipose tissue weight. FC administration significantly reduced lipid accumulation. Moreover, FC could dose-dependently and differentially regulate the expressions of lipid metabolism-related transcription factors. All these data indicated that FC exhibited anti-obesity effects through modulating adipogenesis and lipolysis.

• 생명과학회지
• /
• 제21권9호
• /
• pp.1346-1353
• /
• 2011

산두근(Sophora tonkinensis Gapnep)은 예로부터 동양지역에서 전통적인 약용식물로 사용되어 왔다. 본 연구에서는 3T3-L1 지방전구세포의 성숙지방세포로의 분화와 세포 내 지방생성에 대한 산두근 메탄올 추출물(STME)의 효과와 메커니즘에 대해 조사하였다. STME를 0-200 ${\mu}g$/ml의 농도로 처리한 다음, Oil Red O 염색으로 세포 내축적되는 지방구와 지질의 양을 측정한 결과 농도의존적으로 크게 감소됨을 확인하였으며 3T3-L1 지방전구세포의 분화와 관련된 단백질의 발현의 변화를 조사하였다. 지방세포의 특이적 marker인 peroxisome proliferator-activated receptor ${\gamma}$ (PPAR${\gamma}$), cytidine-cytidine-adenosine-adenosine-thymine (CCAAT)/enhancer-binding proteins ${\alpha}$, ${\beta}$ (C/EBP${\alpha}$, C/EBP${\beta}$) 그리고 sterol regulatory element binding protein (SREBP)의 발현이 STME를 처리하였을 때 현저하게 저해됨을 확인하였다. 세포주기의 변화를 분석한 결과 STME는 지방세포 분화초기 단계인 mitotic clonal expansion 단계에서 G1기로 세포주기를 정지시켰다. 더불어 G1 arrest와 관련된 단백질의 변화를 조사 한 결과, 3T3-L1 세포에 STME를 처리하였을 때 p21의 발현량이 확연하게 증가하였으며, Cdk2, E2F-1 그리고 phosphor-Rb의 발현량은 농도의존적으로 감소하였다. 이러한 결과들에 의하여 STME은 메탄올 추출물임에도 불구하고 3T3-L1 지방전구세포가 성숙지방세포로 분화할 때 G1 arrest를 통하여 지방세포 분화를 억제하며 관련 유전자의 발현 억제도 확연하게 확인할 수 있었으며, 이러한 결과는 항 비만 천연물 소재 탐구의 기초자료로 유용하게 쓰일 것으로 사료된다.

• Ocean and Polar Research
• /
• 제44권1호
• /
• pp.61-67
• /
• 2022

In this study, in order to evaluate the anti-obesity effect of sargassum horneri extract, the effects of the extract on lipase activity and preadipocyte differentiation in 3T3-L1 cells were investigated. S. horneri extract between 0.0 and 1.0 mg/mL showed no cytotoxicity and inhibited lipase activity by 68.1%. When S. horneri extract was utilized at levels of 0.25, 0.5, and 1.0 mg/mL in 3T3-L1 cells, preadipocytes differentiation decreased by 11.4, 19.7, and 25.6%, respectively, showing anti-obesity effects. In addition, after treatment with 1.0 mg/mL S. horneri extract, the mRNA expression levels of sterol regulatory element binding proteins-1c (SREBP-1c), peroxisome proliferator activated receptor-γ (PPAR-γ), CCAAT enhancer binding protein-α (CEBP-α), fatty acid synthase (FAS), and stearoyl-CoA desaturase1 (SCD1) in 3T3-L1 cells were significantly decreased (p < 0.05) by 65.2, 54.9, 50.0, 33.8, and 33.8% respectively. These results showed that S. horneri extract suppresses lipase activity and prophylactic preadipocyte differentiation in 3T3-L1, and thus can be used as an anti-obesity agent in functional foods and medicines.

• Journal of Microbiology and Biotechnology
• /
• 제27권11호
• /
• pp.1925-1931
• /
• 2017

Korean red pine (Pinus densiflora) bark extract, PineXol (PX), was investigated for its potential antioxidant and anti-inflammation effects in vitro. It was hypothesized that PX treatment ($25-150{\mu}g/ml$) would reduce the lipid synthesis in HepG2 hepatocytes as well as lipid accumulation in 3T3-L1 adipocytes. Hepatocytes' intracellular triglycerides and cholesterol were decreased in the PX $150{\mu}g/ml$ treatment group compared with the control (p < 0.05). Consequently, de novo lipogenic proteins (acetyl-CoA carboxylase 1, stearoyl-CoA desaturase 1, elongase of very long chain fatty acids 6, glycerol-3-phosphate acyltransferase 1, and sterol regulatory element-binding protein 1) were significantly decreased in hepatocytes by PX $150{\mu}g/ml$ treatment compared with the control (p < 0.05). In differentiated 3T3-L1 adipocytes, the lipid accumulation was significantly attenuated by all PX treatments (p < 0.01). Regulators of adipogenesis, including CCAAT-enhancer-binding proteins alpha, peroxisome proliferatoractivated receptor gamma, and perilipin, were decreased in PX $100{\mu}g/ml$ treatment compared with the control (p < 0.05). In conclusion, PX might have anti-obesity effects by blocking hepatic lipogenesis and by inhibiting adipogenesis in adipocytes.

• BMB Reports
• /
• 제42권4호
• /
• pp.232-237
• /
• 2009

Sterol regulatory element-binding protein (SREBP)-1c plays a crucial role in the regulation of lipogenic enzymes in the liver. We previously reported that an X-chromosome-linked RNA binding motif (RBMX) regulates the promoter activity of Srebp-1c. However, still unknown was how it regulates the gene expression. To elucidate this mechanism, we screened the cDNA library from mouse liver by yeast two-hybrid assay using RBMX as bait and identified scaffold attachment factor B1 (SAFB1). Immunoprecipitation assay demonstrated binding of SAFB1 to RBMX. Chromatin immunoprecipitation assay showed binding of both SAFB1 and RBMX to the upstream region of Srebp-1c gene. RNA interference of Safb1 reduced the basal and RBMX-induced Srebp-1c promoter activities, resulting in reduced Srebp-1c gene expression. The effect of SAFB1 overexpression on Srebp-1c promoter was found only in the presence of RBMX. These results indicate a major role for SAFB1 in the activation of Srebp-1c through its interaction with RBMX.

• 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
• /
• 제22권3호
• /
• pp.448-458
• /
• 2009

It has been well documented from animal and human studies that conjugated linoleic acid (CLA) has numerous beneficial effects on health. In chickens, CLA exerts many effects on performance ranging from egg quality and yolk lipids to meat quality. Although there are several CLA isomers available, not all CLA isomers have the same incorporation rates into egg yolk: cis-9,trans-11 and trans-10,cis-12 CLA isomers are more favorably deposited into egg yolk than other isomers investigated, but of the two isomers, the former has a higher incorporation rate than the latter. CLA alters the amounts and profiles of lipids in plasma, muscles and liver. Furthermore, increased liver weight was reported in chickens fed dietary CLA. As observed in egg yolk, marked reduction in intramuscular lipids as well as increased protein content was observed in different studies, leading to elevation in protein-to-fat ratio. Inconsistency exists for parameters such as body weight gain, feed intake, feed conversion ratio, egg production rate and mortality, depending upon experimental conditions. One setback is that hard-cooked yolks from CLA-consuming hens have higher firmness as refrigeration time and CLA are increased, perhaps owing to alterations in physico-chemistry of yolk. Another is that CLA can be detrimental to hatchability when provided to breeders: eggs from these breeders have impaired development in embryonic and neonatal stages, and have increased and decreased amounts of saturated fatty acids and monounsaturated fatty acids (MUFAs), respectively. Thus, both problems can be fully resolved if dietary sources rich in MUFAs are provided together with CLA. Emerging evidence suggests that CLA exerts a critical impact on stress and immune functions as it can completely nullify some of the adverse effects produced by immune challenges and reduce mortality in a dose-dependent manner. Finally, CLA is a key regulator of genes that may be responsible for lipid metabolism in chickens. CLA down-regulates both expression of the gene encoding stearoyl-CoA desaturase-1 and its protein activity in the chicken liver while up-regulating mRNA of sterol regulatory element-binding protein-l.

• Asian-Australasian Journal of Animal Sciences
• /
• 제21권1호
• /
• pp.11-18
• /
• 2008

We created a cDNA microarray representing approximately 3,500 pig genes for functional genomic studies. The array elements were selected from 6,494 cDNA clones identified in a large-scale expressed sequence tag (EST) project. These cDNA clones came from normalized and subtracted porcine adipose tissue cDNA libraries. Sequence similarity searches of the 3,426 ESTs represented on the array using BLASTN identified 2,790 (81.4%) as putative human orthologs, with the remainder consisting of "novel" genes or highly divergent orthologs. We used the gene microarray to profile transcripts expressed by adipose tissue of fatty Chinese Xiang pig (XP) and muscley Large White (LW). Microarray analysis of RNA extracted from adipose tissue of fatty XP and muscley LW identified 81 genes that were differently expressed two fold or more. Transcriptional differences of four of these genes, adipocyte fatty acid binding protein (aP2), stearyl-CoA desaturase (SCD), sterol regulatory element binding transcription factor 1 (SREBF1) and lipoprotein lipase (LPL) were confirmed using SYBR Green quantitative RT-PCR technology. Our results showed that high expression of SCD and SREBF1 may be one of the reasons that larger fat deposits are observed in the XP. In addition, our findings also illustrate the potential power of microarrays for understanding the molecular mechanisms of porcine development, disease resistance, nutrition, fertility and production traits.

• 대한한방내과학회지
• /
• 제35권1호
• /
• pp.70-78
• /
• 2014

Objectives : Hoechunyanggyeok-san (HYS) is a traditional herbal medicine, which has been clinically used for treating febrile and inflammatory diseases. HYS has been reported to be a useful treatment for diabetes, atherosclerosis and hyperlipidemia in the type 1 diabetic model. However, the mechanism of the effects of HYS against hyperglycemia and hyperlipidemia is poorly understood. In the present study, we investigated the underlying mechanism of ameliorative effect of HYS on hyperglycemia and hyperlipidemia in vivo. Methods : HYS (10, 50 mg/kg/day, p.o.) was administered every day for 2 weeks to db/db mice and its effect was compared with vehicle-treated db/db mice. To confirm serum glucose and triglyceride (TG) changes, serological testing was performed. The levels of sterol regulatory element-binding protein-1 (SREBP-1) activity and Sirtuin1 (SIRT1), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase ${\alpha}$ ($ACC{\alpha}$) expression were analyzed by western blot analysis. Results : The administration of HYS significantly decreased the elevated serum glucose and TG in db/db mice. HYS administration increased the levels of SIRT1 and AMPK expression compared with the vehicle-treated group. Moreover, HYS treatment significantly inhibited SREBP-1 activity and $ACC{\alpha}$ expression in the liver, while the vehicle-treated group exhibited their increase. Conclusions : In conclusion, HYS is suggested to have an improvement effect on hyperglycemia and hyperlipidemia by activating the SIRT1/AMPK signaling pathway and inhibiting SREBP-1.