• Title/Summary/Keyword: SREBP2

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Anti-Obesity Effect of Schizandrae Fructus Water Extract through Regulation of AMPK/Sirt1/PGC-1α signaling pathway (AMPK/Sirt1/PGC-1α 신호 전달 경로의 조절을 통한 오미자 추출물의 비만 개선 효과)

  • Lee, Se Hui;Park, Hae-Jin;Shin, Mi-Rae;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.37 no.2
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    • pp.1-11
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    • 2022
  • Objectives : Although the anti-obesity effect of Schizandrae Fructus water extract has been demonstrated, its underlying mechanism is still unclear. Therefore, we aimed to evaluate the anti-obesity effect of Schizandrae Fructus water extract through the p-AMP-activated protein kinase (p-AMPK), sirtuin1 (Sirt1), and peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling in 60% high-fat diet (HFD)-induced obese mouse model. Methods : Male C57BL/6 mice were divided into four groups. The Normal group was fed a normal diet and the obese groups were fed 60% HFD. Except for the Control group, the GG group was supplemented with 0.5% Garcinia gummigutta and the SCW group was supplemented with 0.5% Schizandrae Fructus water extract. After 6 weeks, obesity-related biomarkers in serum were measured and the expressions of protein for lipid-related factors in liver tissue were analyzed by western blot. Results : Treatment with SCW significantly down-regulated body weight compared to the Control group. SCW down-regulated levels of triglyceride and total cholesterol in serum and significantly increased p-AMPK, Sirt1, and PGC-1α in liver tissue. In addition, the expressions of fatty acid oxidation-related proteins such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1A (CPT-1A), uncoupling protein 1 (UCP1), and uncoupling protein 3 (UCP3) were significantly up-regulated. However, fatty acid synthesis-related proteins including sterol regulatory element-binding protein-1 (SREBP-1), phospho-Acetyl-CoA Carboxylase (p-ACC), and fatty acid synthase (FAS) were significantly down-regulated. Conclusions : Taken together, SCW treatment showed anti-obesity effect by regulating both fatty acid oxidation-related and fatty acid synthesis-related proteins through AMPK/Sirt1/PGC-1α signaling in 60% HFD-induced obese mice.

Anti-obese Effects and Signaling Mechanisms of Chaenomeles sinensis extracts in 3T3-L1 Preadipocytes and Obese Mice Fed a High-fat Diet (3T3L-1 지방전구세포와 고지방식이로 유도된 비만 마우스 모델에서 모과 추출물의 항비만 효과와 억제 기전)

  • Kim, Da-Hye;Kwon, Bora;Kim, Sang Jun;Kim, HongJun;Jeong, Seung-Il;Yu, Kang-Yeol;Kim, Seon-Young
    • Herbal Formula Science
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    • v.25 no.4
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    • pp.457-469
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    • 2017
  • Obesity is one of the most serious health problem because it induced numerous metabolic syndrome and increases the incidence of various disease, including diabetes, hypertension, dyslipidemia, atherosclerosis, and cancer. In 3T3-L1 adipocytes, increases in reactive oxygens species (ROS) occur with lipid accumulation. NADPH oxidase, producing superoxide anion, may contribute to the development of obesity-associated insulin resistance and type 2 diabetes. In this study, we elucidated the effect of Chaenomeles sinensis koehne extract (CSE) against the development of obesity and the inhibition mechanisms in 3T3-L1 preadiocytes. CSE decreased triglyceride content and inhibited the expression of adipogenic transcription factors including peroxisome proliferator-activated receptor $(PPAR){\gamma}$, CCAT/enhancer binding protein $(C/EBP){\alpha}$ and sterol regulatory element-binding protein (SREBP-1). In addition, CSE highly increased antioxidant activity in a dose-dependent manner. CSE remarkably reduced intracellular ROS increase and NAD(P)H oxidase activity, NOX1, NOX4, Rac1 protein expression, and phosphorylation of p47phox and p67phox We also studied the effect of CSE on weight gain induced by high-fat diet. The oral treatment of CSE (500 mg/kg, body weight) in diet-induced obese (DIO) mice showed decrease in triglyceride and adipocyte size. Therefore, these results indicate that the effect of CSE on anti-obese effects, adipocyte differentiation and reducing triglyceride contents as well as adipocyte size in obese mice, may be associated with inhibition of NAD(P)H oxidase-induced ROS production and adipose transcription factors. These results showed the potential to inhibit the obesity by CSE treatment through controlling the activation of NAD(P)H oxidase in vitro and in vivo obese model.

Effect of Korean Red Ginseng on Hypertriglyceridemia in High Fat/high Cholesterol Diet Rat Model (고지방/고콜레스테롤 식이 랫트 모델에서 홍삼에 의한 고중성지방혈증 개선 효과)

  • Kim, Hye Yoom;Jin, Xian Jun;Hong, Mi Hyeon;Ko, Seon Mi;Hwang, Seung Mi;Im, Dong joong;Ahn, You Mee;Lee, Ho Sub;Kang, Dae Gill;Lee, Yun Jung
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.32 no.1
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    • pp.43-50
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    • 2018
  • Korean Red Ginseng (RG) are used as a traditional treatment for improve blood circulation. This experimental study was designed to investigate the inhibitory effects of Korean red ginseng on lipid metabolism in high fat/cholesterol diet (HFCD)-induced hypertriglyceridemia. Sprague Dawley rats were fed the HFCD diet with/without fluvastatin (Flu, positive control) 3 mg/kg/day, and RG 125 or 250 mg/kg/day, respectively. All groups received regular diet or HFCD diet, respectively, for 13 weeks. The last three groups treatment of Flu and RG 125, and RG 250 orally for a period of 9 weeks. Group 1, reular diet; group 2, HFCD diet; group 3, Flu + HFCD diet; group 4, RG 125 + HFCD diet; group 5, RG 250 + HFCD diet. As a result, treatment with low or high doses of RG markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. RG and Flu also led to an increase in lipoprotein lipase activity in the HFCD group. On the other hand, RG and Flu led to an decrease in fatty acid synthase and free fatty acid activity in the HFCD group. Treatment with RG suppressed increased expressions of $PPAR-{\alpha}$ and AMPK in HFCD rat liver or muscle. In addition, the RG attenuated triglyceridemia by inhibition of $PPAR-{\gamma}$ and FABP protein expression levels and LXR and SREBP-1 gene expression in liver or muscle. The RG significantly prevented the development of the metabolic disturbances such as hypertriglyceridemia and hyperlipidemia. Taken together, the administration of RG improves hypertriglyceridemia through the alteration in suppression of triglyceride synthesis and accentuated of triglyceride decomposition. These results suggested that RG is useful in the prevention or treatment of hypertriglyceridemia.

Studies on Antioxidant and Anti-hyperlipidemic Effects in Induced Hypercholesterolemic Rats of Steamed Achyranthis Bidentatae Radix (우슬(牛膝)의 증숙(蒸熟)에 따른 항산화 효능 및 고지혈증 유발 흰쥐에 대한 고지혈증 개선 효능에 대한 연구)

  • Kim, Jeong-Soo;Park, MyungJae;Kim, SuJi;Shin, Mi-Rae;Lee, AhReum;Park, Hae-Jin;Roh, Seong-Soo;Seo, Young Bae
    • The Korea Journal of Herbology
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    • v.33 no.6
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    • pp.43-60
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    • 2018
  • Objectives : This study was conducted to compare the effect of Achyranthis Bidentatae Radix on antioxidant changes and antihyperlipidemics in hypercholesterolemic rats according to changes in the number of steams. Methods : The experimental animals were divided into six groups: normal (Nor), high cholesterol diet (Veh), high cholesterol diet with Simvastatin 5 mg/kg (Sim), high cholesterol diet with AR0 extract 200 mg/kg (AR0), high cholesterol diet with AR6 extract 200 mg/kg (AR6) and high cholesterol diet plus AR9 extract 200 mg/kg (AR9). I measured HDL, LDL TC, TG contents and ROS from each serums and compared them. I analyzed antioxidant-related protein expressions and cholesterol-related protein expressions in each liver tissues. I also performed optical microscopic analysis through liver tissue staining. Results : The Antioxidant activity of Achyranthis Bidentatae Radix was increased by steaming processes. In vivo, AR0 decreased liver weight in hyperlipidemic rats. LDL TC, TG, AI and CRF were decreased but HDL was increased in AR0. AST, ALT, creatinine, and BUN were decreased in AR0. ROS was decreased in AR0, AR6, and AR9. SOD, catalase and GPx were decreased by steaming processes. p-AMPK was decreased but SREBP-2, p-ACC, and HMGCR were increased by steaming processes. Histologic analysis showed that AR0 decreased liver fat accumulation. Conclusion : In conclusion, AR0 can be developed as a treatment for hyperlipemia. And it is required to research on antioxidant effect changes among different times steamed Achyranthis Bidentatae Radix.

The effects of Allomyrina dichotoma larval extract on palmitate-induced insulin resistance in skeletal muscle cells (장수풍뎅이 유충 추출물이 고지방산 처리 골격근세포의 인슐린 저항성에 미치는 영향)

  • Kim, Kyong;Sim, Mi-Seong;Kwak, Min-Kyu;Jang, Se-Eun;Oh, Yoon Sin
    • Journal of Nutrition and Health
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    • v.55 no.4
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    • pp.462-475
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    • 2022
  • Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

Antioxidant and antiobesity activities of oral treatment with ethanol extract from sprout of evening primrose (Oenothera laciniata) in high fat diet-induced obese mice (달맞이순 (Oenothera laciniata) 에탄올 추출물 섭취가 고지방식이로 유도한 비만 마우스에서 항산화 및 비만억제효과)

  • Kwak, Chung Shil;Kim, Mi-Ju;Kim, Sun Gi;Park, Sunyeong;Kim, In Gyu;Kang, Heun Soo
    • Journal of Nutrition and Health
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    • v.52 no.6
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    • pp.529-539
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    • 2019
  • Purpose: Sprouts of evening primrose (Oenothera laciniata, OL) were reported to have high contents of flavonoids and potent antioxidant activity. This study examined the antioxidant and antiobesity activities of OL sprouts to determine if they could be a natural health-beneficial resource preventing obesity and oxidative stress. Methods: OL sprouts were extracted with 50% ethanol, evaporated, and lyophilized (OLE). The in vitro antioxidant activity of OLE was examined using four different tests. The antiobesity activity and in vivo antioxidant activity from OLE consumption were examined using high fat diet-induced obese (DIO) C57BL/6 mice. Results: The IC50 for the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging and superoxide dismutase (SOD)-like activities of OLE were 26.2 ㎍/mL and 327.6 ㎍/mL, respectively. OLE exhibited the ferric reducing antioxidant power (FRAP) activity of 56.7 ㎍ ascorbic acid eq./mL at 100 ㎍/mL, and an increased glutathione level by 65.1% at 200 ㎍/mL compared to the control in the hUC-MSC stem cells. In an animal study, oral treatment with 50 mg or 100 mg of OLE/kg body weight for 14 weeks reduced the body weight gain, visceral fat content, fat cell size, blood leptin, and triglyceride levels, as well as the atherogenic index compared to the high fat diet control group (HFC) (p < 0.05). The blood malondialdehyde (MDA) level and the catalase and SOD-1 activities in adipose tissue were reduced significantly by the OLE treatment compared to HFC as well (p < 0.05). In epididymal adipose tissue, the OLE treatment reduced the mRNA expression of leptin, PPAR-γ and FAS significantly (p < 0.05) compared to HFC while it increased adiponectin expression (p < 0.05). Conclusion: OLE consumption has potent antioxidant and antiobesity activities via the suppression of oxidative stress and lipogenesis in DIO mice. Therefore, OLE could be a good candidate as a natural resource to develop functional food products that prevent obesity and oxidative stress.

Effects of High Stocking Density on the Expression of Metabolic Related Genes in Two Strains of Chickens (닭의 고밀도사양 스트레스가 품종 간 체내대사 유전자 발현에 미치는 영향)

  • Sohn, Sea Hwan;Jang, In Surk;An, Young Sook;Moon, Yang Soo
    • Korean Journal of Poultry Science
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    • v.42 no.1
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    • pp.51-59
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    • 2015
  • Chickens are exposed to the external and internal stressors such as low and high temperature, high stocking density, feed restriction and disease. There have been a few studies on gene expressions through the investigation of chickens under direct exposure to the stress of high stocking density. The objective of the present study was to determine the expressions of genes associated with stress, endoplasmic reticulum (ER)-stress, lipid and glucose metabolism in two strains of chickens, Korean Native Chicken (KNC) and White Leghorn (WL), raised in high stocking density. A total of 164 chickens aged 40 weeks were randomly allotted to a $540cm^2/bird$ stocking density (control), whereas the chickens in a high density group were assigned in a $311cm^2/bird$ stocking density with feeding ad libitum for 10 weeks. Total RNA was extracted from the live for qRT-PCR. The expression levels of hsp70 and $hsp90{\alpha}$ were higher in WL subjected to stress with high stocking density compared with those genes in control (P<0.05), while the expressions of genes were not affected in KNC. ER stress marker gene XBP1 was also highly expressed in WL with stress (P<0.05), but the stress of high stocking density did not influence to ER stress marker genes in KNC. Lipid metabolism associated genes including FABP4, FATP1 and ACSL1 were highly expressed in WL compared with KNC when subjected to high stocking density stress (P<0.05). The expression of glucose transport gene GLUT2 and GLUT8 were increased in chickens exposured to the stress of high stocking density (P<0.05). The data indicate that WL is more sensitive to the stress of high stocking density compared with KNC and the stress may influence the modulation of lipid and glucose metabolism in the liver of chickens.

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.

Inhibitory effect of water-soluble mulberry leaf extract on hepatic lipid accumulation in high-fat diet-fed rats via modulation of hepatic microRNA-221/222 expression and inflammation (고지방식이 급여 쥐에서 수용성 뽕나무 잎 추출물의 간 microRNA-221/222 발현 및 염증 조절을 통한 간 지질 축적억제 효과)

  • Lee, Mak-Soon;Kim, Cheamin;Ko, Hyunmi;Kim, Yangha
    • Journal of Nutrition and Health
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    • v.55 no.2
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    • pp.227-239
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    • 2022
  • Purpose: This study investigated the effects of water-soluble mulberry leaf extract (ME) on hepatic lipid accumulation in high-fat diet-fed rats via the regulation of hepatic microRNA (miR)-221/222 and inflammation. Methods: Male Sprague-Dawley rats (4 weeks old) were randomly divided into 3 groups (n = 7 each) and fed with 10 kcal% low-fat diet (LF), 45 kcal% high-fat diet (HF), or HF + 0.8% ME for 14 weeks. Lipid profiles and cytokine levels of the liver and serum were measured using commercial enzymatic colorimetric and enzyme-linked immunosorbent assay, respectively. The messenger RNA (mRNA) and miR levels in liver tissue were assayed by real-time quantitative reverse-transcription polymerase chain reaction. Results: Supplementation of ME reduces body weight and improves the liver and serum lipid profiles as compared to the HF group. The mRNA levels of hepatic peroxisome proliferator-activated receptor-gamma, sterol regulatory element binding protein-1c, fatty acid synthase, and fatty acid translocase, which are genes involved in lipid metabolism, were significantly downregulated in the ME group compared to the HF group. In contrast, the mRNA level of hepatic carnitine palmitoyl transferase-1 (involved in fatty acid oxidation) was upregulated by ME supplementation. Furthermore, administration of ME significantly downregulated the mRNA levels of inflammatory mediators such as hepatic tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1, and inducible nitric oxide synthase. The serum levels of TNF-α, IL-6, and nitric oxide were also significantly reduced in ME group compared to the HF group. Expression of hepatic miR-221 and miR-222, which increase in the inflammatory state of the liver, were also significantly inhibited in the ME group compared to the HF group. Conclusion: These results indicate that ME has the potential to improve hepatic lipid accumulation in high-fat diet-fed rats via modulation of inflammatory mediators and hepatic miR-221/222 expressions.