Abstract | BACKGROUND: The diet-induced obesity model of zebrafish (DIO-zebrafish) share 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: 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.
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Authors | Y Shimada, J Kuroyanagi, B Zhang, M Ariyoshi, N Umemoto, Y Nishimura, T Tanaka |
Journal | International journal of obesity (2005)
(Int J Obes (Lond))
Vol. 38
Issue 8
Pg. 1053-60
(Aug 2014)
ISSN: 1476-5497 [Electronic] England |
PMID | 24254064
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Mxd3 protein, mouse
- Repressor Proteins
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Topics |
- 3T3-L1 Cells
- Adipocytes
(metabolism)
- Animals
- Cell Differentiation
- Dimerization
- Down-Regulation
- Gene Knockdown Techniques
- Intra-Abdominal Fat
(metabolism)
- Mice
- Obesity
(genetics, metabolism, physiopathology)
- Repressor Proteins
(genetics, metabolism)
- Zebrafish
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