• Title/Summary/Keyword: SREBP

Search Result 231, Processing Time 0.03 seconds

Expressional Evaluation of C/EBP Family, SREBP1, and Steroid Hormone Receptors in the Epididiymal Fat of Postnatally Developing Mouse

  • Lee, Yong-Seung;Lee, Ki-Ho
    • Development and Reproduction
    • /
    • v.26 no.2
    • /
    • pp.49-58
    • /
    • 2022
  • The differentiation and development of preadipocyte into mature adipocyte are regulated by transcription factors, such as CCAAT enhancer binding protein (Cebp) gene family and sterol regulatory element binding transcription factor 1 (Srebp1). Steroid hormones give influences on the development and function of adipocyte. The present research examined expression patterns of CCAAT enhancer binding protein alpha (Cebpa), CCAAT enhancer binding protein beta (Cebpb), CCAAT enhancer binding protein gamma (Cebpg), sterol regulatory element binding transcription factor 1 (Srebp1), androgen receptor (Ar), and estrogen receptors (Esr) among different epididymal fat parts during postnatal period by quantitative real-time polymerase chain reaction. In the distal epididymal fat, expression of Cebpa, Cebpb, Cebpg, Srebp1, Ar, and Esr2 was increased until 12 months of age, while expression of Esr1 was decreased at 5 months of age and was not detectable after 8 months of age. In the proximal epididymal fat, transcript levels of Cebps and Srebp1 were increased at 8 months of age, followed by decreases of Cebpb and Cebpg transcript levels at 12 months of age. An additional increase of Srebp1 expression was observed at 12 months of age. Expression of Ar and Esr2 were increased until 8 months of age, followed by a drop of Ar expression level at 12 months of age. Expression pattern of Esr1 was similar to that in the distal epididymal fat. In the tail epididymal fat, expression of Cebpa, Cebpg, Srebp1, Ar, and Esr2 was increased with age. Esr1 was not detectable at all. The highest level of Cebpb was observed at 8 months of age. These data suggest the possibility of developmental and functional differentiation among the epididymal fat parts.

Glucose and Insulin Stimulate Lipogenesis in Porcine Adipocytes: Dissimilar and Identical Regulation Pathway for Key Transcription Factors

  • Zhang, Guo Hua;Lu, Jian Xiong;Chen, Yan;Dai, Hong Wei;ZhaXi, YingPai;Zhao, Yong Qing;Qiao, Zi Lin;Feng, Ruo Fei;Wang, Ya Ling;Ma, Zhong Ren
    • Molecules and Cells
    • /
    • v.39 no.11
    • /
    • pp.797-806
    • /
    • 2016
  • Lipogenesis is under the concerted action of ChREBP, SREBP-1c and other transcription factors in response to glucose and insulin. The isolated porcine preadipocytes were differentiated into mature adipocytes to investigate the roles and interrelation of these transcription factors in the context of glucose- and insulin-induced lipogenesis in pigs. In ChREBP-silenced adipocytes, glucose-induced lipogenesis decreased by ~70%, however insulin-induced lipogenesis was unaffected. Moreover, insulin had no effect on ChREBP expression of unperturbed adipocytes irrespective of glucose concentration, suggesting ChREBP mediate glucose-induced lipogenesis. Insulin stimulated SREBP-1c expression and when SREBP-1c activation was blocked, and the insulin-induced lipogenesis decreased by ~55%, suggesting SREBP-1c is a key transcription factor mediating insulin-induced lipogenesis. $LXR{\alpha}$ activation promoted lipogenesis and lipogenic genes expression. In ChREBP-silenced or SREBP-1c activation blocked adipocytes, $LXR{\alpha}$ activation facilitated lipogenesis and SREBP-1c expression, but had no effect on ChREBP expression. Therefore, $LXR{\alpha}$ might mediate lipogenesis via SREBP-1c rather than ChREBP. When ChREBP expression was silenced and SREBP-1c activation blocked simultaneously, glucose and insulin were still able to stimulated lipogenesis and lipogenic genes expression, and $LXR{\alpha}$ activation enhanced these effects, suggesting $LXR{\alpha}$ mediated directly glucose- and insulin-induced lipogenesis. In summary, glucose and insulin stimulated lipogenesis through both dissimilar and identical regulation pathway in porcine adipocytes.

Cannabidiol Inhibits Lipogenesis by Regulating Akt/AMPK-SREBP-1 Pathway in Sebocytes (피지세포에서 Akt/AMPK-SREBP-1 경로를 통한 CBD의 피지 합성 억제 효능)

  • Yoon Gyung Kwon;Ji Young Yoon;Hanon Lee;Dong Hyo Kim;Jun Hyo Lee;Diane M Thiboutot;Dae Hun Suh;Byoung Jun Park
    • Journal of Life Science
    • /
    • v.33 no.4
    • /
    • pp.343-348
    • /
    • 2023
  • Acne is one of the most common skin diseases, mainly occurring in adolescence. The pathophysiology of acne involves not only hormonal, genetic and environmental factors, but also other factors including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and overgrowth of Cutibacterium acnes (C. acnes). Cannabidiol (CBD) is known to relieve pain, stress and inflammation. Moreover, cannabis extracts containing CBD have been reported to be effective in treating acne. However, the therapeutic effect of CBD on acne remains unclear. Therefore, this study aimed to investigate the effect and mechanism of CBD on lipogenesis in SEB-1 sebocytes. We treated sebocytes with CBD and found that it not only inhibited lipid synthesis, but also inhibited cell proliferation by inducing apoptosis. We then demonstrated that sterol response element-binding protein-1 (SREBP-1) mediates the inhibitory effect of CBD on lipogenesis. Furthermore, Akt and adenosine monophosphate-activated protein kinase (AMPK), upstream regulators of SREBP-1, were regulated by CBD treatment. Taken together, our studies demonstrate that CBD inhibits adipogenesis by regulating the Akt/AMPK-SREBP-1 signaling pathway, providing potential for use as a therapeutic agent for acne. Further research is needed to confirm the effect of CBD on inflammation caused by hyperkeratosis, which will increase the possibility of using CBD for acne treatment.

Arctii Lappa Fructus Extract Induces Lipogenesis through SREBP-1 Activation of Sebocytes (피지선세포에서 SREBP-1 활성에 의한 우방자추출물의 지질 생성 촉진 작용)

  • In, Myung Hee;Mun, Yeun Ja;Woo, Won Hong
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.34 no.1
    • /
    • pp.1-6
    • /
    • 2020
  • Arctii Lappa Fructus has the numerous health benefits, including antioxidant, anti-inflammatory, and anti-carcinogenic properties. Skin lipids are one of several factors that maintain epidermal barrier function. This study was to explore the lipogenic effect by ethanol extract of Arctii Lappa Fructus (EAF) in sebocytes. First, it was confirmed that EAF exhibited high antioxidant activity and collagenase activity inhibition. We found that cholesterol and triglyceride levels of cells by EAF were increased significantly in a dose-dependent manner. Moreover, EAF increased the expression of transcription factor sterol regulatory element-binding protein-1 (SREBP-1) in the cells. These results suggest that EAF induces lipogenesis in cells through the activation of SREBP-1.

Ponciri Fructus Extract Induces Lipogenesis through Transcription Factor SREBP-1 Activation (지실 추출물의 전사인자 SREBP-1 활성에 의한 지질 생성 촉진)

  • Kim, Dae-Sung;Jeon, Byoung-Kook;Mun, Yeun-Ja;Lee, Ghang-Tai;Lee, Kun-Kuk;Woo, Won-Hong
    • YAKHAK HOEJI
    • /
    • v.56 no.4
    • /
    • pp.268-273
    • /
    • 2012
  • This study was to explore the lipogenic effect by ethanol extract of ponciri fructus (EPF) and possible molecular mechanisms in sebocyte. When SZ95 sebocyte cell line were treated with the EPF, lipid droplets were accumulated in the majority of cells. EPF increased expression of sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) in the SZ95 cells. EPF augmented expression of PPAR-${\beta}$ and PPAR-${\gamma}$ but not that of PPAR-${\alpha}$. These results suggest that EPF induces lipogenesis in SZ95 cells through SREBP-1, PPAR-${\beta}$ and PPAR-${\gamma}$ activations.

Policosanol Reduces Blood Cholesterol Levels by Inhibiting Sterol Regulatory Element-binding Proteins-1c and Fatty Acid Synthase (Sterol regulatory element-binding proteins-1c와 지방산 합성효소의 억제를 통한 폴리코사놀의 혈중 콜레스테롤 감소)

  • Min Jung Park;Byeong Min An;Dongjun Lee;Ji Myung Choi;Yung Hyun Choi;Bo Sun Joo
    • Journal of Life Science
    • /
    • v.33 no.4
    • /
    • pp.315-324
    • /
    • 2023
  • The underlying action of policosanol in lowering cholesterol level has not yet been clearly elucidated. Several recent studies have suggested that sterol regulatory element-binding proteins (SREBP)-1c play a role in the regulation of cholesterol synthesis via the fatty acid synthesis pathway. To date, no study has evaluated the effects of policosanol on SREBP-1c-mediated fatty acid synthesis. Therefore, this study aimed to investigate whether the SREBP-1c-mediated fatty acid biosynthetic pathway is associated with the cholesterol-lowering effects of policosanol. Seven-week-old C57BL/6 male mice were randomly divided into 7 groups (n=7 per group) and treated for 8 weeks as follows: 1) normal diet (normal control), 2) high-fat diet (HFD), 3) HFD+ethanol (Pol-0), 4) HFD+policosanol 1 mg/kg (Pol-1), 5) HFD+policosanol 2 mg/kg (Pol-2), 6) HFD+policosanol 4 mg/kg (Pol-4), and 7) HFD+simvastatin 50 ㎍/kg (positive control). Policosanol and simvastatin were administered at the same time every day while maintaining the HFD. Body weight and food intake were measured weekly for 8 weeks. After 8 weeks, serum cholesterol levels were measured, histological analysis was carried out, and the expressions of SREBP-1c and fatty acid synthase (FAS) in the liver tissues were examined. Policosanol reduced body weight and the amount of food intake in a dose-dependent manner. Serum cholesterol levels were significantly lowered in the Pol-1 and Pol-4 groups. The expression of SREBP-1c and FAS was also significantly decreased in the Pol-4 group. These results suggest that the cholesterol-lowering effects of policosanol can occur due to the inhibition of the expression of SREBP-1c and FAS.

Kaurenoic acid, a natural substance from traditional herbal medicine, alleviates palmitate induced hepatic lipid accumulation via Nrf2 activation

  • Han, Changwoo
    • The Journal of Korean Medicine
    • /
    • v.41 no.4
    • /
    • pp.64-71
    • /
    • 2020
  • Objectives: This study was done to look into whether Nrf2 take some role in the anti-lipogenic effect of kaurenoic acid in a nonalcoholic fatty liver disease (NAFLD) cellular model. Materials and Methods: We measured the effect of kaurenoic acid on intracellular steatosis and Nrf2 activation. Next, the effect of kaurenoic acid on SREBP-1c and some lipogenic genes in palmitate treated HepG2 cells with or without Nrf2 silencing. Results: The increased SREBP-1c expression was significantly decreased by concomitant kaurenoic acid treatment in non-targeting negative control siRNA transfected HepG2 cells. However, kaurenoic acid did not significantly inhibited increased SREBP-1c level in Nrf2 specific siRNA transfected HepG2 cells Conclusions: Kaurenoic acid has a potential to activate Nrf2, which may suppress SREBP-1c mediated intracellular steatosis in HepG2 cells.

Inhibitory Activity of Wild-Simulated Ginseng against Non-Alcoholic Fatty Liver Disease in HepG-2 Cells (산양삼(Wild-Simulated Ginseng)의 비알코올성 지방간 억제활성)

  • So Jung Park;Yurry Um;Min Yeong Choi;Jin Boo Jeong
    • Korean Journal of Plant Resources
    • /
    • v.36 no.1
    • /
    • pp.26-31
    • /
    • 2023
  • In this study, we investigated in vitro inhibitory activity of wild-simulated ginseng (WSG) against non-alcoholic fatty liver disease using HepG-2 cells. T0901317 treatment increased the lipid accumulation in HepG-2 cells, but WSG treatment inhibited T0901317-mediated lipid accumulation. In addition, WSG downregulated T0901317-mediated expression of SREBP-1c, ACC, FAS and SCD-1 protein. In addition, WSG increased the phosphorylation level of LKB1 and AMPK. Compound C treatment blocked WSG-mediated downregulation of SREBP-1c protein. In conclusion, WSG is considered to inhibit the accumulation of lipids and triglycerides in HepG-2 cells by inducing the activation of LKB1 and AMPK successively, thereby reducing the expression of FAS, ACC, and SCD-1 through suppression of SREBP-1c expression.

SAFB1, an RBMX-binding protein, is a newly identified regulator of hepatic SREBP-1c gene

  • Omura, Yasushi;Nishio, Yoshihiko;Takemoto, Tadashi;Ikeuchi, Chikako;Sekine, Osamu;Morino, Katsutaro;Maeno, Yasuhiro;Obata, Toshiyuki;Ugi, Satoshi;Maegawa, Hiroshi;Kimura, Hiroshi;Kashiwagi, Atsunori
    • BMB Reports
    • /
    • v.42 no.4
    • /
    • 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.

Eriobotrya japonica inhibits the transactivation of nuclear orphan receptor : the possibility to treat the chronic diseases (비파엽의 핵수용체 관련 신규 약물 작용점 연구 : 만성 질환 치료 가능성)

  • Min-Jin, Kim;Young Woo, Kim;Sun-Dong, Park
    • Herbal Formula Science
    • /
    • v.30 no.4
    • /
    • pp.225-231
    • /
    • 2022
  • Objectives : Oxidative damage has a variety of mechanism in the human organs including brain and liver. The purpose of this study is to examine the prevention against cellular damage, and the inhibitory effect on lipogenesis of the water extract of Eriobotrya japonica (EJE). Methods : The effect of EJE on cell viability was assessed using the MTT assay. To investigate the mechanism of EJE's inhibition of lipogenesis, we analyzed the relevant proteins using immunoblot analysis. Results : Induction of T0901317, a LXR agonist, significantly increased SREBP-1c expression, which was blocked by the pretreatment of EJE in the dose-dependent manners. This beneficial herb also regulated the genes related with SREBP-1c such as the acetyl-CoA carboxylase. Conclusion : These results suggested that EJE might have a possibility of the treatment of chronic diseases as mediated with the inhibition of LXRα/SREBP-1c pathway.