Since the publication of the world's first zebrafish model of dietary obesity in 2011, we have used this model to elucidate various drug screening methods and novel mechanisms of visceral fat accumulation and fatty liver development.
Various related technologies were also developed, such as blood sampling without killing, oral administration of test materials, measurement of visceral fat content using CT imaging, and measurement of food intake.
We have achieved various research outcomes using this model.
For example, we have reported for the first time in the world that the mxd3 gene contributes to the accumulation of visceral fat, and have successfully identified multiple anti-obesity compounds derived from natural products.
In addition, we successfully constructed the world's first type 2 diabetes model using zebrafish in 2017. We discovered the analysis of the gut microbiota in this zebrafish and the involvement of the cenpx gene in insulin secretion. Currently, we are further improving this model for research on diabetes-related conditions.
In 2020, we successfully achieved downsizing of DIO-zebrafish and established a model for visceral fat accumulation using juvenile zebrafish. The use of adult zebrafish in DIO experiments allowed for various analyses comparable to mouse models, including evaluation of body weight gain, visceral fat content, analysis of neutral lipids, total cholesterol, fatty liver, and liver parameters. However, conducting tests with a large number of animals, such as 100 animals at once, was labor-intensive.
By using zebrafish juveniles at 3 weeks post-fertilization, measuring 1-2 cm in length, this labor-intensive process was improved, and assays with up to 5 animals per well in a 6-well plate became possible. The red regions in the images represent visceral fat, which can be observed through in vivo imaging. We are currently utilizing this model for screening assays and identification of active compounds from natural products.
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