• Title/Summary/Keyword: $LXR{\alpha}$

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Expressional Regulation of Replication Factor C in Adipocyte Differentiation (지방세포분화에서의 replication factor C 단백질의 발현조절)

  • Cho, Hyun-Kook;Kim, Hye-Young;Yu, Hyun-Jeong;Cheong, Jae-Hun
    • Journal of Life Science
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    • v.21 no.2
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    • pp.202-210
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    • 2011
  • Adipocyte differentiation is an ordered multistep process requiring the sequential activation of several groups of adipogenic transcription factors, including CCAAT/enhancer-binding protein-$\alpha$ and peroxisome proliferator-activated receptor-$\gamma$, and coactivators. In previous reports, we identified that replication factor C 140 (RFC140) protein played a critical role in regulating adipocyte differentiation as a coactivator. Here, we show expressional regulation of RFC140 and small RFC subunit, RFC38, following characterization of gene promoter of RFC140 and RFC38. In addition, RFC140 increases PPAR$\gamma$-mediated gene activation, resulting from direct protein-protein interaction of RFC140 and PPAR$\gamma$. Taken together, these findings demonstrate that the regulated expression of RFC140 and RFC38 by specific adipocyte transcription factors is required for the adipocyte differentiation process.

Effects of Samhwangsasim-tang on obesity-related metabolic disease in mice (삼황사심탕(三黃瀉心湯)이 수컷 생쥐의 비만(肥滿) 관련 대사질환(代謝疾患)에 미치는 영향)

  • Lee, Ju-Young;Kook, Yoon-Bum
    • Herbal Formula Science
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    • v.22 no.1
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    • pp.93-104
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    • 2014
  • Objectives : Samhwangsasim-tang (SHSST) is a traditional Korean medication, which has been used in Korea for treatment of hypertension and chest pain. Hyperlipidemia and inflammation could influence hypertension and chest pain. This study investigated whether and how SHSST reduces the hyperlipidemia and inflammation related to high-cholesterol diet-induced obesity in rats. Methods : Mice were divided randomly into four groups: the normal diet group, high-cholesterol diet group, low dose treatment group supplemented with 30% ethanol extract of SHSST (L) and high dose treatment group supplemented with 80% ethanol extract of SHSST (H). L and H groups were orally administered with SHSST at the dose of 50mg/kg a day respectively and others were administered with the same volume of physiological saline. Results : Administration of SHSST resulted in a decrease in serum levels of total cholesterol and low-density lipoprotein. Expression of hepatic genes(SREBP2, LXR, LDLR, and HMG-CoA) related with cholesterol metabolism was also suppressed. In addition, SHSST decreased the expression of inflammation-related gene (TNF-${\alpha}$, IL-6, ICAM-1, VCAM-1, TGF-${\beta}1$ and fibronectin). Histological examinations also showed that the size of the adipocytes was smaller in the SHSST treated group than in the high-colesterol diet group. In an in vitro study, SHSST inhibited the production of nitric oxide in a concentration-dependent manner. Conclusions : This study indicates that SHSST has anti-hyperlipidemia and anti-inflammatory effects. It may also suggest that SHSST may be alternative therapy for treatment of hyperlipidemia and its complications.

Effects of disturbed liver growth and oxidative stress of high-fat diet-fed dams on cholesterol metabolism in offspring mice

  • Kim, Juyoung;Kim, Juhae;Kwon, Young Hye
    • Nutrition Research and Practice
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    • v.10 no.4
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    • pp.386-392
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    • 2016
  • BACKGROUND/OBJECTIVES: Changes in nutritional status during gestation and lactation have detrimental effects on offspring metabolism. Several animal studies have shown that maternal high-fat diet (HFD) can predispose the offspring to development of obesity and metabolic diseases, however the mechanisms underlying these transgenerational effects are poorly understood. Therefore, we examined the effect of maternal HFD consumption on metabolic phenotype and hepatic expression of involved genes in dams to determine whether any of these parameters were associated with the metabolic outcomes in the offspring. MATERIALS/METHODS: Female C57BL/6 mice were fed a low-fat diet (LFD: 10% calories from fat) or a high-fat diet (HFD: 45% calories from fat) for three weeks before mating, and during pregnancy and lactation. Dams and their male offspring were studied at weaning. RESULTS: Dams fed an HFD had significantly higher body and adipose tissue weights and higher serum triglyceride and cholesterol levels than dams fed an LFD. Hepatic lipid levels and mRNA levels of genes involved in lipid metabolism, including $LXR{\alpha}$, SREBP-2, FXR, LDLR, and ABCG8 were significantly changed by maternal HFD intake. Significantly lower total liver DNA and protein contents were observed in dams fed an HFD, implicating the disturbed liver adaptation in the pregnancy-related metabolic demand. HFD feeding also induced significant oxidative stress in serum and liver of dams. Offspring of dams fed an HFD had significantly higher serum cholesterol levels, which were negatively correlated with liver weights of dams and positively correlated with hepatic lipid peroxide levels in dams. CONCLUSIONS: Maternal HFD consumption induced metabolic dysfunction, including altered liver growth and oxidative stress in dams, which may contribute to the disturbed cholesterol homeostasis in the early life of male mice offspring.

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.

Enrichment of Short-Chain Ceramides and Free Fatty Acids in the Skin Epidermis, Liver, and Kidneys of db/db Mice, a Type 2 Diabetes Mellitus Model

  • Kim, Minjeong;Jeong, Haengdueng;Lee, Buhyun;Cho, Yejin;Yoon, Won Kee;Cho, Ahreum;Kwon, Guideock;Nam, Ki Taek;Ha, Hunjoo;Lim, Kyung-Min
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.457-465
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    • 2019
  • Patients with diabetes mellitus (DM) often suffer from diverse skin disorders, which might be attributable to skin barrier dysfunction. To explore the role of lipid alterations in the epidermis in DM skin disorders, we quantitated 49 lipids (34 ceramides, 14 free fatty acids (FFAs), and cholesterol) in the skin epidermis, liver, and kidneys of db/db mice, a Type 2 DM model, using UPLC-MS/MS. The expression of genes involved in lipid synthesis was also evaluated. With the full establishment of hyperglycemia at the age of 20 weeks, remarkable lipid enrichment was noted in the skin of the db/db mice, especially at the epidermis and subcutaneous fat bed. Prominent increases in the ceramides and FFAs (>3 fold) with short or medium chains ($LXR{\alpha}/{\beta}$ and $PPAR{\gamma}$, nuclear receptors promoting lipid synthesis, lipid synthesis enzymes such as elongases 1, 4, and 6, and fatty acid synthase and stearoyl-CoA desaturase were highly expressed in the skin and livers of the db/db mice. Collectively, our study demonstrates an extensive alteration in the skin and systemic lipid profiles of db/db mice, which could contribute to the development of skin disorders in DM.