Publication List Japanese

化学工業 Vol.68No.7 ゼブラフィッシュ創薬とInternet of Zebrafish(IoZ)

月刊ファームステージ Vol.17 No.2 ゼブラフィッシュ創薬とフェノミクス薬理学

NEW薬理学 改訂第7版 プロテオーム創薬

三重大学春秋会会報 第39号 ゼブラフィッシュ創薬への道程 

理系マイナビ special interview

》Cross-species transcriptome analyses discovered MXD3 regulation in visceral adiposity


Cross-species transcriptome analyses discovered MXD3 regulation in visceral adiposity


○島田康人1-5)、有吉美稚子1) 、廣田智一1) 、黒?淳哉1)、梅本紀子1),2)、西村有平1-5)、田中利男1-5)

1) 三重大学大学院医学系研究科薬理ゲノミクス
2) 三重大学大学院医学系研究科システムズ薬理学
3) メディカルゼブラフィッシュ研究センター
4) 生命科学研究支援センター機能ゲノミクス分野バイオインフォマティクス部門
5) 新産業創成拠点メディカルケモゲノミクス研究室

The diet-induced obesity model of zebrafish (DIO-zebrafish) shares a common pathophysiological pathway with mammalian obesity (BMC Physiology, 2010). To identify genes related to visceral adiposity, we conducted transcriptome analyses of human and zebrafish obese populations using the GEO and DNA microarray, and found that MXD3 expression was increased. We then intraperitoneally injected morpholino antisense oligonucleotides (mxd3-MO) to knockdown mxd3 expression in DIO-zebrafish. Mxd3-MO suppressed the increase in body weight, visceral fat accumulation, and the size of mature adipocytes. Subsequently, dyslipidemia and liver steatosis were also ameliorated by mxd3-MO. In mouse 3T3-L1 cells, Mxd3 shRNA inhibited preadipocyte proliferation and adipocyte maturation. qPCR analyses showed that the early differentiation marker, Cebpd and late differentiation markers (Cebpb and Pparg) were downregulated by Mxd3 knockdown in 3T3-L1 cells and DIO-zebrafish.
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.