• Title/Summary/Keyword: sterol regulatory element binding protein 1

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Antioxidant and Anti-Obesity Effects of Juglans mandshurica in 3T3-L1 Cells and High-Fat Diet Obese Rats

  • Da-Hye Choi;Min Hong;Tae-Hyung, Kwon;Soo-Ung Lee
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.634-643
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    • 2024
  • Juglans mandshurica Maxim. walnut (JMW) is well-known for the treatment of dermatosis, cancer, gastritis, diarrhea, and leukorrhea in Korea. However, the molecular mechanism underlying its antiobesity activity remains unknown. In the current study, we aimed to determine whether JMW can influence adipogenesis in 3T3-L1 preadipocytes and high-fat diet rats and determine the antioxidant activity. The 20% ethanol extract of JMW (JMWE) had a total polyphenol content of 133.33 ± 2.60 mg GAE/g. Considering the antioxidant capacity, the ABTS and DPPH values of 200 ㎍/ml of JMWE were 95.69 ± 0.94 and 79.38 ± 1.55%, respectively. To assess the anti-obesity activity of JMWE, we analyzed the cell viability, fat accumulation, and adipogenesis-related factors, including CCAAT-enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein-1c (SREBP1c), peroxisome proliferator-activated receptor-gamma (PPARγ), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC). We found that total lipid accumulation and triglyceride levels were reduced, and the fat accumulation rate decreased in a dose-dependent manner. Furthermore, JMWE suppressed adipogenesis-related factors C/EBPα, PPARγ, and SREBP1c, as well as FAS and ACC, both related to lipogenesis. Moreover, animal experiments revealed that JMWE could be employed to prevent and treat obesity-related diseases. Hence, JMWE could be developed as a healthy functional food and further explored as an anti-obesity drug.

Inhibitory Effects of Chrysanthemum boreale Makino on 3T3-L1 Preadipocyte Differentiation and Down-regulation of Adipogenesis and Lipogenesis (산국(Chrysanthemum boreale Makino) 꽃 유래 에센셜오일(Essential oil)이 지방세포 분화 및 지방생성에 미치는 영향)

  • Hwang, Dae Il;Choi, In-Ho;Kim, Do Yoon;Park, Soo Min;Kim, Ha Bin;Li, YaLi;Lee, Hwan Myung
    • Journal of Life Science
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    • v.29 no.3
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    • pp.332-336
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    • 2019
  • Obesity is associated with an increased risk of many diseases including type 2 diabetes mellitus, hypertension, and hyperlipidemia. The flowers of Chrysanthemum boreale have been used as traditional medicines for the treatment of diseases such as obesity and type 2 diabetes mellitus. This study aimed to evaluate the effect of C. boreale Makino flower essential oil (CFEO) on adipocyte differentiation using preadipocyte cell line 3T3-L1. CFEO at concentrations between 0.1 and $5{\mu}g/ml$ did not affect 3T3-L1 cell viability. A CFEO concentration of between 0.1 and $1{\mu}g/ml$ significantly inhibited lipid accumulation during MDI-induced differentiation in 3T3-L1 cells in a dose-dependent manner, reaching a maximal level at $1{\mu}g/ml$ ($28.94{\pm}2.01%$; approximately 30% of control treated with MDI alone). Western blot analysis revealed that CFEO concentrations between 0.1 and $1{\mu}g/ml$ suppressed the activations of three adipogenic transcription factors in the MDI-stimulated 3T3-L1 cells: peroxisome proliferator-activated receptor ${\gamma}$; CCATT/enhancer binding protein ${\alpha}$; and sterol regulatory element binding protein-1. Moreover, the expressions of lipogenic enzymes, acetyl-CoA carboxylase, and fatty acid synthase were also inhibited by treatment with CFEO between 0.1 and $1{\mu}g/ml$. CFEO may therefore be a promising functional material for obesity prevention.

Anti-Obesity Effects of Menthae Herba Hydrosol on High-Fat Diet Induced Obese Mice (고지방 식이로 유도된 비만 생쥐에서 박하 Hydrosol의 항비만 효과)

  • Soo-Min Choi;So-Young Kim;Young-Jun Kim;Chang-Hoon Woo;Mi-Ryeo Kim;Hee-Duk An
    • Journal of Korean Medicine Rehabilitation
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    • v.33 no.3
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    • pp.33-46
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    • 2023
  • Objectives We investigated anti-obesity effects of Menthae Herba hydrosol in obese mice. Methods Animals were divided into four groups, and treatments were performed for 7 weeks. After the treatment, serum lipid profiles, weight and pathological morphology in liver, kidney, adipose tissue were measured. Also, hepatic protein and gene expression levels of lipid metabolism-related factors were analyzed. Results Body weight was decreased in P3% group. In P1% (group fed high-fat diet and 1% Menthae Herba hydrosol) and P3% (group fed high-fat diet and 3% Menthae Herba hydrosol) group, weight of white adipose tissue, serum levels of triglyceride and blood urea nitrogen were decreased, and weight of muscle was increased. Also, liver, kidney and epididymal adipocyte size were reduced in P1% and P3% group. Adenosine monophosphate-activated protein kinase was increased and sterol regulatory element binding protein-1c (SREBP-1c) was decreased in P3% group. mPeroxisome proliferator-activator receptor-γ, mMonocyte chemotactic protein-1 were decreased in P1% and P3% group. In P3% group, mSREBP-1c was decreased and mCarnitine palmitoyl transferase-1 was increased. And mUncoupling protein 1 in brown adipose tissue was increased. Conclusions These results suggest that Menthae Herba hydrosol has a worthy effect on anti-obesity.

Effects of Panicum miliaceum L. extract on adipogenic transcription factors and fatty acid accumulation in 3T3-L1 adipocytes

  • Park, Mi-Young;Seo, Dong-Won;Lee, Jin-Young;Sung, Mi-Kyung;Lee, Young-Min;Jang, Hwan-Hee;Choi, Hae-Yeon;Kim, Jae-Hyn;Park, Dong-Sik
    • Nutrition Research and Practice
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    • v.5 no.3
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    • pp.192-197
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    • 2011
  • The dietary intake of whole grains is known to reduce the incidence of chronic diseases such as obesity, diabetes, cardiovascular disease, and cancer. To investigate whether there are anti-adipogenic activities in various Korean cereals, we assessed water extracts of nine cereals. The results showed that treatment of 3T3-L1 adipocytes with Sorghum bicolor L. Moench, Setaria italica Beauvois, or Panicum miliaceum L. extract significantly inhibited adipocyte differentiation, as determined by measuring oil red-O staining, triglyceride accumulation, and glycerol 3-phosphate dehydrogenase activity. Among the nine cereals, P. miliaceum L. showed the highest anti-adipogenic activity. The effects of P. miliaceum L. on mRNA expression of peroxisome proliferator-activated receptor-${\gamma}$, sterol regulatory element-binding protein 1, and the CCAAT/enhancer binding protein-${\alpha}$ were evaluated revealing that the extract significantly decreased the expression of these genes in a dose-dependent manner. Moreover, P. miliaceum L. extract changed the ratio of monounsaturated fatty acids to saturated fatty acids in adipocytes, which is related to biological activity and cell characteristics. These results suggest that some cereals efficiently suppress adipogenesis in 3T3-L1 adipocytes. In particular, the effect of P. miliaceum L. on adipocyte differentiation is associated with the downregulation of adipogenic genes and fatty acid accumulation in adipocytes.

Vitamin C Inhibits Visceral Adipocyte Hypertrophy and Lowers Blood Glucose Levels in High-Fat-Diet-Induced Obese C57BL/6J Mice

  • Park, Younghyun;Jang, Joonseong;Lee, Dongju;Yoon, Michung
    • Biomedical Science Letters
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    • v.24 no.4
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    • pp.311-318
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    • 2018
  • Vitamin C (ascorbic acid) supplementation has been suggested to negatively correlate with obesity in humans and other animals. Previous studies, including ours, have demonstrated that a high-fat diet (HFD) induces obesity and related diseases such as hyperlipidemia, hyperglycemia, insulin resistance, and nonalcoholic fatty liver disease. Here, we investigated the effects of vitamin C on visceral adipocyte hypertrophy and glucose intolerance in C57BL/6J mice. Mice received a low-fat diet (LFD, 10% kcal fat), HFD (45% kcal fat), or the same HFD supplemented with vitamin C (HFD-VC, 1% w/w) for 15 weeks. Visceral adiposity and glucose intolerance were examined using metabolic measurements, histology, and gene expression analyses. Mice in the HFD-VC supplementation group had reduced body weight, mesenteric fat mass, and mesenteric adipocyte size compared with HFD-fed mice. Vitamin C intake in obese mice also decreased the mRNA levels of lipogenesis-related genes (i.e., stearoyl-CoA desaturase 1 and sterol regulatory element-binding protein 1c) in mesenteric adipose tissues, inhibited hyperglycemia, and improved glucose tolerance. In addition, vitamin C attenuated the HFD-induced increase in the size of pancreatic islets. These results suggest that vitamin C suppresses HFD-induced visceral adipocyte hypertrophy and glucose intolerance in part by decreasing the visceral adipose expression of genes involved in lipogenesis.

A Comparative Study on Anti-Obesity Efficacy of Cydonia oblonga Miller Fruit Extract in Diet-Induced Obesity Animal Models (식이유도 비만 동물모델에서 마르멜로추출물의 항비만 효능 비교 연구)

  • Jung Soon Hwang;Myeong Oh Hwang;Kisung Kwon;Eun Ji Kim
    • Journal of Korean Medicine for Obesity Research
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    • v.24 no.1
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    • pp.13-24
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    • 2024
  • Objectives: The objective of this study was to explore the anti-obesity effect of Cydonia oblonga Miller fruit extract (COME) and to compare its anti-obesity efficacy with Garcinia cambogia extract (GCE) in diet-induced obese mice. Methods: Five-week-old male C57BL/6 were allocated into four groups: control diet (CD), high-fat diet (HFD), HFD + 400 mg/kg body weight (BW)/day COME (H+C), or HFD + 400 mg/kg BW/day GCE (H+G) groups. COME or GCE was administered once a day by oral gavage for eight weeks. Body weight, body fat percentage, fat weight, and biochemical parameters in serum were measured. The expressions of transcription factors and their target genes in epididymal adipose tissues were analyzed by reverse transcription polymerase chain reaction. Results: COME reduced body weight, weight gain, body fat percentage, total white adipose tissue weight, adipocyte size, and serum levels of insulin and leptin in high-fat diet-induced obese C57BL/6 mice. COME suppressed the mRNA expressions of CCAAT/enhancer binding proteinα, peroxisome proliferator-activated receptorγ, sterol-regulatory element-binding protein-1c, fatty acid synthase, and adipocyte protein 2 and increased carnitine palmitoyl transferase 1 mRNA expression in epidydimal adipose tissues. The anti-obesity efficacy of COME was found to be similar to that of GCE at the same dose. However, COME more effectively decreased adipose tissue weights, epididymal adipocyte size, serum insulin and leptin compared to GCE. Conclusions: These results demonstrated that COME is not toxic and exhibits anti-obesity efficacy at a level similar to that of GCE, suggesting that COME may be applicable as an anti-obesity agent.

Histone deacetylase inhibition attenuates hepatic steatosis in rats with experimental Cushing's syndrome

  • Kim, Mina;Lee, Hae-Ahm;Cho, Hyun-Min;Kang, Seol-Hee;Lee, Eunjo;Kim, In Kyeom
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.1
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    • pp.23-33
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    • 2018
  • Cushing's syndrome (CS) is a collection of symptoms caused by prolonged exposure to excess cortisol. Chronically elevated glucocorticoid (GC) levels contribute to hepatic steatosis. We hypothesized that histone deacetylase inhibitors (HDACi) could attenuate hepatic steatosis through glucocorticoid receptor (GR) acetylation in experimental CS. To induce CS, we administered adrenocorticotropic hormone (ACTH; 40 ng/kg/day) to Sprague-Dawley rats by subcutaneous infusion with osmotic mini-pumps. We administered the HDACi, sodium valproate (VPA; 0.71% w/v), in the drinking water. Treatment with the HDACi decreased steatosis and the expression of lipogenic genes in the livers of CS rats. The enrichment of GR at the promoters of the lipogenic genes, such as acetyl-CoA carboxylase (Acc), fatty acid synthase (Fasn), and sterol regulatory element binding protein 1c (Srebp1c), was markedly decreased by VPA. Pan-HDACi and an HDAC class I-specific inhibitor, but not an HDAC class II a-specific inhibitor, attenuated dexamethasone (DEX)-induced lipogenesis in HepG2 cells. The transcriptional activity of Fasn was decreased by pretreatment with VPA. In addition, pretreatment with VPA decreased DEX-induced binding of GR to the glucocorticoid response element (GRE). Treatment with VPA increased the acetylation of GR in ACTH-infused rats and DEX-induced HepG2 cells. Taken together, these results indicate that HDAC inhibition attenuates hepatic steatosis through GR acetylation in experimental CS.

Glucosamine increases macrophage lipid accumulation by regulating the mammalian target of rapamycin signaling pathway

  • Sang-Min Kim;Dong Yeol Kim;Jiwon Park;Young-Ah Moon;Inn-Oc Han
    • BMB Reports
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    • v.57 no.2
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    • pp.92-97
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    • 2024
  • Elevated blood glucose is associated with an increased risk of atherosclerosis. Data from the current study showed that glucosamine (GlcN), a normal glucose metabolite of the hexosamine biosynthetic pathway (HBP), promoted lipid accumulation in RAW264.7 macrophage cells. Oleic acid- and lipopolysaccharide (LPS)-induced lipid accumulation was further enhanced by GlcN in RAW264.7 cells, although there was no a significant change in the rate of fatty acid uptake. GlcN increased acetyl CoA carboxylase (ACC), fatty acid synthase (FAS), scavenger receptor class A, liver X receptor, and sterol regulatory element-binding protein-1c (SREBP-1c) mRNA expression, and; conversely, suppressed ATP-binding cassette transporter A1 (ABCA-1) and ABCG-1 expression. Additionally, GlcN promoted O-GlcNAcylation of nuclear SREBP-1 but did not affect its DNA binding activity. GlcN stimulated phosphorylation of mammalian target of rapamycin (mTOR) and S6 kinase. Rapamycin, a mTOR-specific inhibitor, suppressed GlcN-induced lipid accumulation in RAW264.7 cells. The GlcN-mediated increase in ACC and FAS mRNA was suppressed, while the decrease in ABCA-1 and ABCG-1 by GlcN was not significantly altered by rapamycin. Together, our results highlight the importance of the mTOR signaling pathway in GlcN-induced macrophage lipid accumulation and further support a potential link between mTOR and HBP signaling in lipogenesis.

Cissus quadrangularis Extracts Decreases Body Fat Through Regulation of Fatty acid Synthesis in High-fat Diet-induced Obese Mice

  • Lee, Hae Jin;Lee, Dong-Ryung;Choi, Bong-Keun;Park, Sung-Bum;Jin, Ying-Yu;Yang, Seung Hwan;Suh, Joo-Won
    • Journal of Applied Biological Chemistry
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    • v.59 no.1
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    • pp.49-56
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    • 2016
  • The current study investigated the anti-obesity effect of Cissus quadrangularsis extracts (CQR-300) and its molecular action mechanism on obese mice induced high-fat diet (HFD). To induce the obesity, mice were fed a HFD for 6 weeks and then fed HFD only or HFD with CQR-300 at 50 and 200 mg/kg. Then, body weight gain and white adipose tissue weights were measured. We investigated the reduction in body fat and the regulation of fatty acid synthesis was measured by dual energy X-ray absorptiometry and real-time PCR with Western blot, respectively. In vitro study, CQR-300 inhibited pancreatic lipase activity. The CQR-300 treatment was significantly decreased the body weight gain and adipocytes size as well as white adipose tissues weights in HFD-induced obese mice. Furthermore, CQR-300 reduced the body fat and fat mass with regulating of adipose tissue hormones as leptin. Treatment with 50 mg/kg CQR-300 showed effectively lower expression levels of adipogenesis/lipogenesis related genes and proteins such as CCAAT/enhancer binding protein ${\alpha}$ ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor ${\gamma}$ ($PPAR{\gamma}$), Sterol regulatory element binding protein-1c (SREBP-1c), and fatty acid synthase (FAS) in white adipose tissue (WAT) as compared with the HFD fed only mice. These results suggest that the CQR-300 has an anti-obesity effect via inhibition of lipase activity, decrease the body fat mass by regulating the adipogenesis and lipogenesis related genes and proteins in epididymal adipose tissue with evaluate body fat reduce in the HFD-induced obese mice.

Temporal Changes in the Hepatic Fatty Liver in Mice Receiving Standard Lieber-DeCarli Diet

  • Yin, Hu-Quan;Lee, Byung-Hoon
    • Toxicological Research
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    • v.24 no.2
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    • pp.113-117
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    • 2008
  • Chronic exposure to ethanol induces cumulative damage to the liver starting from fatty infiltration to cirrhosis depending on the dose and duration of exposure. The whole process leading to the development of alcoholic liver disease is very complex and the mechanisms involved are not fully understood. Among many experimental animal models, Lieber-DeCarli liquid diet provides moderate to severe pathophysiological outcome depending on the compositional changes. In the present study, we investigated the temporal changes in the early phase hepatic disease in rats fed with standard Lieber-DeCarli diet. Male Wistar rats were fed with Lieber-Decarli ethanol diet for 6 weeks and the liver samples were obtained after 2, 4 and 6 weeks. Mild fatty infiltration was observed in 2 weeks of feeding and it became evident in 4 and 6 week samples. The level of hepatic triglyceride showed a good agreement with the data obtained in the pathological analysis. Feeding mice with ethanol diet resulted in the maturation and translocation of SREBP-1 to nucleus in the liver. Western blot analysis of the pooled liver sample of control and ethanol fed animals showed a clear-cut time-dependent increase in the expression of nSREBP-1. These data provide important information for selecting proper time point in experimental intervention study in the field of drug development for alcoholic liver disease.