ＭＺＴ（株）ゼブラフィッシュ創薬研究所

Cross-species transcriptome analyses discovered MXD3 regulation in visceral adiposity

第87回日本薬理学会年会
Cross-species transcriptome analyses discovered MXD3 regulation in visceral adiposity

食餌性ゼブラフィッシュ肥満とヒト臨床肥満の統合トランスクリプトーム解析による新規内臓脂肪制御遺伝子MXD3の発見

○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.

ＭＺＴ（株）ゼブラフィッシュ創薬研究所

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Cross-species transcriptome analyses discovered MXD3 regulation in visceral adiposity