• Title/Summary/Keyword: SREBP1c

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Crude Extract and Solvent-Partitioned Fractions of the Halophyte Atriplex gmelinii Inhibit Adipogenesis in 3T3-L1 Preadipocytes (3T3-L1 지방전구세포에서 염생식물 Atriplex gmelinii의 조추출물과 용매 분획물의 지방세포분화 억제)

  • Jung Im Lee;Jung Hwan Oh;Chang-Suk Kong;Youngwan Seo
    • Journal of Korean Medicine for Obesity Research
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    • v.23 no.2
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    • pp.69-77
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    • 2023
  • Objectives: Atriplex gmelinii C. A. Meyer is a halophyte belonging to the Chenopodiaceae family, and its young leaves and stems are used as fodder for livestock. The aim of the present study was to investigate the effects of A. gmelinii extract and its solvent fractions on lipid accumulation during adipogenesis of 3T3-L1 preadipocytes. Methods: The samples of A. gmelinii were separately extracted using methylene chloride and methanol. Subsequently, they were combined to formulate the initial extract, which was then partitioned based on polarity to prepare solvent fractions. Oil Red O staining was employed to measure lipid accumulation during the differentiation of 3T3-L1 preadipocytes. To verify cytotoxicity in 3T3-L1 cells, MTT assays were conducted. The expression levels of transcription factors in 3T3-L1 preadipocytes were measured through Western blotting analysis. Results: At 50 ㎍/mL, treatment of A. gmelinii extract and its solvent fractions during the differentiation of 3T3-L1 preadipocytes significantly diminished lipid accumulation with no noteworthy cytotoxicity on cell viability. Additionally, when investigating the biochemical pathways that underlie the prevention of lipid accumulation using solvent fractions, it was found that the n-BuOH and n-hexane fractions significantly decreased the expression of key transcription factors involved in the generation of fat, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and sterol regulatory element-binding protein-1c (SREBP1c). Conclusions: These findings indicate that A. gmelinii can effectively reduce the accumulation of fat in 3T3-L1 adipocytes, making it a potentially valuable material for mitigating and preventing obesity.

Effects of Unripe Black Raspberry Water Extract on Lipid Metabolism and Oxidative Stress in Mice (복분자 미숙과 물 추출물이 마우스의 지질대사 및 산화적 스트레스에 미치는 영향)

  • Choi, Hye Ran;Lee, Jung-Hyun;Lee, Su Jung;Lee, Min Jung;Jeong, Jong Tae;Lee, Tae-Bum
    • Korean Journal of Food Science and Technology
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    • v.46 no.4
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    • pp.489-497
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    • 2014
  • We examined the effects of unripe black raspberry water extract (UBR-W) on lipid metabolism and oxidative stress in mice. C57BL/6J mice were divided into 4 groups: those administered a control diet (CTL), high-fat diet (HFD), UBR-W and simvastatin for 12 weeks. In the HFD group, LDL cholesterol were significantly higher than in the CTL group. However, the UBR-W treated group showed dose-dependent reduction of plasma LDL levels. Hepatic total lipid, TC, and malondialdehyde were significantly increased in hyperlipidemic mice. However, supplementation with either UBR-W or simvastatin effectively reduced these lipid profiles and lipid peroxidation. UBR-W increased mRNA expression of the LDL receptor, sterol regulatory element binding protein 2 (SREBP2), 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase and ATP-binding cassette transporter A1 (ABCA1) compared to that observed in the HFD group. In addition, UBR-W and simvastatin showed significantly reduced oxidized LDL uptake by the scavenger receptor CD36. These results suggest that UBR-W is useful for treatment and prevention of hyperlipidemia and lipid peroxidation.

Development of Lotus Root Bugak with Plasma Lipid Reduction Capacity by Addition of Opuntia ficus-indica var. saboten or Green Tea as a Coloring Agent (백년초 및 녹차 가루 첨가 연근 부각의 지질저하 기능성)

  • Kim, Mijeong;Hong, Sun Hee;Chung, Lana;Choe, Eunok;Song, Yeong-Ok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.333-340
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    • 2014
  • The purpose of this study was to develop functional lotus root bugak with plasma lipid reduction capacity by controlling the color of batter used for bugak preparation. Lotus root, nearly colorless, was selected to observe color effects. Gardeniae fructus (GF), Opuntia ficus-indica var. saboten (OF), and green tea (GT), which are colored yellow, red, and green, respectively, were used as coloring agents. Fermented glutinous rice was prepared naturally during winter season by placing glutinous rice and water (1:2, w/w) together in a crock pot for 7 days. Coloring materials (10%, w/w) were blended with glue made from fermented glutinous rice flour to prepare the batter. Cooked lotus root was then mixed with a 1.1-fold amount of batter (w/w) and dried at room temperature. Lotus root bugak (LRB) is pan-fried with un-roasted sesame oil, which is traditionally used as frying oil in Korea. Low-density lipoprotein receptor knockout ($LDLr^{-/-}$) mice (n=36) were fed an atherogenic diet (AD) containing various types of LRB (10 g%) for 10 weeks. Plasma triglyceride, total cholesterol, and LDL-C concentrations decreased significantly in mice fed LRB prepared with OF batter (OFB) and GT batter (GTB) (P<0.05). Protein expression levels of fatty acid synthase (FAS) and 3-hydroxyl-3-methylglutaryl coenzyme A reductase (HMGCR) in the OFB and GTB groups were suppressed compared with the LRB group (P<0.05). In accordance with the results on FAS and HMGCR expression, sterol regulatory element binding protein-I and II (SREBP-I and II), which are responsible for the regulation of FAS and HMGCR gene expression, respectively, were down-regulated compared to the LRB group (P<0.05). In conclusion, the plasma lipid reduction activities of OFB and GTB could be mediated through down-regulation of FAS and HMGCR mRNA expression via suppression of regulatory molecules, SREBP-I and II, in $LDLr^{-/-}$ mice.

Anti-obesity Effects of Peucedanum japonicum Thunberg L. on 3T3-L1 Cells and High-fat Diet-induced Obese Mice (식방풍잎(Peucedanum japonicum Thunberg L.)의 물추출물이 3T3-L1 세포와 고지방식이로 유도된 마우스에서 항비만 효과)

  • Jung, Ho-Kyung;Sim, Mi-Ok;Jang, Ji-Hun;Kim, Tae-Muk;An, Byeong-Kwan;Kim, Min-Suk;Jung, Won Seok
    • Korean Journal of Plant Resources
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    • v.29 no.1
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    • pp.1-10
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    • 2016
  • Obesity is a pro-inflammatory state that contributes to the development of metabolic disorders such as hyperlipidemia, insulin resistance, type 2 diabetes, non-alcoholic fatty liver, and cardiovascular disease. In this study, we evaluated the inhibition of adipogenesis in 3T3-L1 cells and in high-fat diet (HFD)-induced obese mice by Peucedanum japonicum Thunberg L. water extract (PJT). Lipid accumulation measurement indicates that PJT markedly inhibited adipogenesis in a dose-dependent manner. RT-PCR results demonstrated that the mRNA expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor-γ (PPARγ) and CCAAT/enhancer binding protein-α (C/EBPα) in 3T3-L1 cells were significantly down-regulated by PJT treatment. Oral administration of PJT (100, 300, and 500 ㎎/㎏, b.w/daily for 4 weeks) was conducted in high-fat diet induced obese mice and C57BL/6 mice. The PJT-administered group of HFD-induced mice had a lower body weight gain, along with decreased serum levels of glucose, triglycerides, and total cholesterol compared with the control mice, however, the HDL-cholesterol/total cholesterol ratio was increased. Furthermore, the elevated mRNA expression levels of adipogenesis related genes in the white adipose tissue of obese mice were significantly suppressed by PJT. These results indicate that PJT exhibits anti-obesity effects in obese mice by decreasing in serum lipid levels and lipogenesis related gene.

The Anti-obesity Effects of Younggyechulgam-tang-ga Hwanggi on Obesity in Mice Induced by High Fat Diet (고지방식이 유도 비만생쥐에 대한 영계출감탕(苓桂朮甘湯) 가(加) 황기(黃芪)의 항비만 효과)

  • Jeong, Man-Jin;Woo, Chang-Hoon;Ahn, Hee-Duk
    • 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.

Improvement of Lipid Homeostasis Through Modulation of Low-density Lipoprotein Receptor Family by Functional Ingredients (천연 기능성 물질(Functional Ingredients)을 활용한 LDL 수용체과(科) 조절과 지질항상성 개선)

  • Jeong, Jeongho;Ryu, Yungsun;Park, Kibeum;Go, Gwang-woong
    • Food Engineering Progress
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    • v.21 no.1
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    • pp.1-11
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    • 2017
  • Dyslipidemia, defined as elevated triglyceride (TG), total- and LDL-C, and/or decreased HDL-C levels, is considered a principal risk factor for cardiovascular disease. The low-density lipoprotein receptor (LDLR) family has been considered a key player in the prevention of dyslipidemia. The LDLR family consists of cytoplasmic membrane proteins and plays an important role not only in ligand-receptor binding and uptake, but also in various cell signaling pathways. Emerging reports state that various functional ingredients dynamically modulate the function of the LDLR family. For instance, oats stimulated the LDLR function in vivo, resulting in decreased body weight and improved serum lipid profiles. The stimulation of LRP6 by functional ingredients in vitro activated the Wnt/${\beta}-catenin$ pathway, subsequently suppressing the intracellular TG via inhibition of SREBP1, $PPAR{\gamma}$, and $C/EBP{\alpha}$. Furthermore, the extract of Cistanchetubulosa enhanced the expression of the mRNA of VLDLR, followed by a reduction in the serum cholesterol level. In addition, fermented soy milk diminished TG and total cholesterol levels while increasing HDL-C levels via activation of LRP1. To summarize, modulating the function of the LDLR family by diverse functional ingredients may be a potent therapeutic remedy for the treatment of dyslipidemia and cardiovascular diseases.

Allium hookeri Extract Improves Type 2 Diabetes Mellitus in C57BL/KSJ Db/db Obese Mouse via Regulation of Hepatic Lipogenesis and Glucose Metabolism (삼채 추출물의 인슐린 저항성 개선 효과 및 기전 탐색)

  • Kim, Ji-Soo;Heo, Jin-Sun;Choi, Jong-Won;Kim, Gun-Do;Sohn, Kie-Ho
    • 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.

Ethanol Extracts of Mori Folium Inhibit Adipogenesis Through Activation of AMPK Signaling Pathway in 3T3-L1 Preadipocytes (3T3-L1 세포에서 상엽이 유발하는 AMPK signaling pathway를 통한 adipogenesis 억제에 관한 연구)

  • Ji, Seon Young;Jeon, Keong Yoon;Jeong, Jin Woo;Hong, Su Hyun;Huh, Man Kyu;Choi, Yung Hyun;Park, Cheol
    • Journal of Life Science
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    • v.27 no.2
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    • pp.155-163
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    • 2017
  • Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.

Effects of Taeeumjowuitanggagam-bang on the Expression of Adipocytokines and SREBPs in Liver of db/db Mouse (태음조위탕가감방(太陰調胃湯加減方)의 db/db 마우스 간(肝)에 대한 아디포사이토카인 및 SREBPs의 발현에 미치는 영향)

  • Baek, Jong-Woo;Jeong, Mi-Kyung;Ko, Seong-Gyu;Jun, Chan-Yong;Park, Jong-Hyeong;Choi, You-Kyung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.24 no.6
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    • pp.989-995
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    • 2010
  • The aim of this study was to investigate the effect of Taeeumjowuitanggagam-bang(TJV) on the mRNA expression of adipocytokines (TNF-${\alpha}$ and IL-6), and SREBPs. Mice were divided into 4 groups ; a normal group of db/+ mice, a control group of db/db mice, a group (db/db mice) treated with TJV 200 mg/kg, and a group (db/db mouse) treated with TJV 500 mg/kg. They were treated orally with TJV and measured their body weight every other day during 9 weeks. After that, we measured the mRNA expression of adipocytokines (TNF-${\alpha}$ and IL-6) and SREBPs (SREBE-1a and SREBP-1c) in liver, and blood concentration of total cholesterol, triglyceride, too. In addition, liver samples were fixed in 4% PFA for 2 hours and stored in $-70^{\circ}C$. Liver tissues were embedded in Optical cutting temperature(OCT) compound and 30 ${\mu}m$ sections were cut. Tissue sections were stained Oil-Red-O to visualize neutral lipids. Nuclei were stained with hematoxylin solution. In result, the TJV reduced the mRNA expressions of TNF-${\alpha}$ and IL-6 and SREBPs in liver and stained liver tissue less red than control group. However, there was no significant differences in total cholestreol and triglyceride blood concentration and body weight among groups. The TJV has inhibitory effect on the mRNA expression of adipocytokines and SREBPs. Therefore, it is assumed that the TJV is related to inhibiting lipogenesis in the liver

Transcriptional Regulation of Lipogenesis and Adipose Expansion (Lipogenesis와 adipose expansion의 전사조절)

  • Jang, Younghoon
    • Journal of Life Science
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    • v.32 no.4
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    • pp.318-324
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    • 2022
  • PPARγ and C/EBPα are master adipogenic transcription factors (TFs) required for adipose tissue development. They control the induction of many adipocyte genes and the early phase of adipogenesis in the embryonic development of adipose tissue. Adipose tissue continues to expand after birth, which, as a late phase of adipogenesis, requires the lipogenesis of adipocytes. In particular, the liver and adipose tissues are major sites for de novo lipogenesis (DNL), where carbohydrates are primarily converted to fatty acids. Furthermore, fatty acids are esterified with glycerol-3-phosphate to produce triglyceride, a major source of lipid droplets in adipocytes. Hepatic DNL has been actively studied, but the DNL of adipocytes in vivo remains not fully understood. Thus, an understanding of lipogenesis and adipose expansion may provide therapeutic opportunities for obesity, type 2 diabetes, and metabolic diseases. In adipocytes, DNL gene expression is transcriptionally regulated by lipogenesis coactivators, as well as by lipogenic TFs such as ChREBP and SREBP1a. Recent in vivo studies have revealed new insights into the lipogenesis gene expression and adipose expansion. Future detailed molecular mechanism studies will determine how nutrients and metabolism regulate DNL and adipose expansion. This review will summarize recent updates of DNL in adipocytes and adipose expansion in terms of transcriptional regulation.