MZT(株)ゼブラフィッシュ創薬研究所

  • HOME
  • 研究開発
  • メンバー
  • アルバム
  • リンク
  • 研究員募集
  • アクセス
  • HOME
  • >
  • Publication List English
  • >
  • 詳細

最近の記事

2019/02/18
Toxicological Evaluation of SiO2 Nanoparticles by Zebrafish Embryo Toxicity Test
2018/12/27
Increased susceptibility to oxidative stress-induced toxicological evaluation by genetically modified nrf2a-deficient zebrafish.
2018/01/18
EGF receptor kinase suppresses ciliogenesis through activation of USP8 deubiquitinase
2017/11/23
Chemokines protect vascular smooth muscle cells from cell death induced by cyclic mechanical stretch.
2017/07/29
New photic stimulating system with white light-emitting diodes to elicit electroretinograms from zebrafish larvae.
2017/03/09
Potential protective function of the sterol regulatory element binding factor 1-fatty acid desaturase 12 axis in early-stage age-related macular degeneration
2016/07/11
Activation of Sterol Regulatory Element Binding Factors by Fenofibrate and Gemfibrozil Stimulates Myelination in Zebrafish
2016/06/14
Downregulation of GSTK1 Is a Common Mechanism Underlying Hypertrophic Cardiomyopathy
2016/06/07
Comparative Transcriptome Analysis Identifies CCDC80 as a Novel Gene Associated with Pulmonary Arterial Hypertension
2016/06/06
Establishment of a drug evaluation model against light-induced retinal degeneration using adult pigmented zebrafish

一覧に戻る

2013/11/20
  • CiteULike
  • reddit
  • StumbleUpon
  • linkedin
  • Delicious
  • Mendeley
  • はてなブックマーク
  • Youtube
  • Google+
  • Twitter
  • Facebook

Downregulation of max dimerization protein 3 is involved in decreased visceral adipose tissue by inhibiting adipocyte differentiation in zebrafish and mice.

International Journal of Obesity (Lond). 2013 Nov 20. doi: 10.1038/ijo.2013.217. [Epub ahead of print]

Downregulation of max dimerization protein 3 is involved in decreased visceral adipose tissue by inhibiting adipocyte differentiation in zebrafish and mice.

Shimada Y, Kuroyanagi J, Zhang B, Ariyoshi M, Umemoto N, Nishimura Y, Tanaka T.

1] Department of Molecular and Cellular Pharmacology, Pharmacogenomics and Pharmacoinformatics, Mie University Graduate School of Medicine, Mie, Japan [2] Department of Systems Pharmacology, Mie University Graduate School of Medicine, Mie, Japan [3] Mie University Medical Zebrafish Research Center, Mie, Japan [4] Department of Bioinformatics, Mie University Life Science Research Center, Mie, Japan [5] Department of Omics Medicine, Mie University Industrial Technology Innovation, Mie, Japan.



Abstract


Background:The diet-induced obesity model of zebrafish (DIO-zebrafish) shares a common pathophysiological pathway with mammalian obesity.Objectives:We aimed to investigate the role of Max dimerization protein 3 (MXD3) in visceral fat accumulation and adipocyte differentiation, by conducting knockdown experiments using zebrafish and mouse preadipocytes.Methods:To identify genes related to visceral adiposity, we conducted transcriptome analyses of human and zebrafish obese populations using the Gene Expression Omnibus and DNA microarray. We then intraperitoneally injected morpholino antisense oligonucleotides (MO-mxd3) to knockdown mxd3 gene expression in DIO-zebrafish and measured several parameters, which reflected human obesity and associated metabolic diseases. Finally, lentiviral Mxd3 shRNA knockdown in mouse 3T3-L1 preadipocytes was conducted. Quantitative PCR analyses of several differentiation markers were conducted during these gene knockdown experiments.Results:We found that MXD3 expression was increased in the obese population in humans and zebrafish. Intraperitoneal MO-mxd3 administration to DIO-zebrafish suppressed the increase in body weight, visceral fat accumulation, and the size of mature adipocytes. Subsequently, dyslipidemia and liver steatosis were also ameliorated by MO-mxd3. In mouse adipocytes, Mxd3 expression was drastically increased in the early differentiation stage. Mxd3 shRNA inhibited preadipocyte proliferation and adipocyte maturation. Quantitative PCR analyses showed that the early differentiation marker, CCAAT/enhancer-binding protein delta (Cebpd) and late differentiation markers (CCAAT/enhancer-binding protein, alpha and peroxisome proliferator-activated receptor gamma) were downregulated by Mxd3 knockdown in 3T3-L1 cells and DIO-zebrafish. Subsequently, mature adipocyte markers (adiponectin and caveolin 1 for zebrafish, and fatty acid binding protein 4 and stearoyl-coenzyme A desaturase 1 for mouse adipocytes) were also decreased.Conclusion:Mxd3 regulates preadipocyte proliferation and early adipocyte differentiation via Cebpd downregulation in vitro and in vivo. Integrated analysis of human and zebrafish transcriptomes allows identification of a novel therapeutic target against human obesity and further associated metabolic disease.International Journal of Obesity accepted article preview online, 20 November 2013. doi:10.1038/ijo.2013.217.


PMID: 24254064 [PubMed - as supplied by publisher]

関連リンク

  • International Journal of Obesity
  • PubMed

関連ファイル

  • 【PDF】Downregulation of max dimerization protein 3 is involved in decreased visceral adipose tissue by inhibiting adipocyte differentiation in zebrafish and mice.