Rodent models of obesity can be used to address the systemic and multi-organ effects of excessive fat storage, but smaller animals are more suitable for large-scale genetic screening. However, measuring crucial metabolic parameters such as blood glucose, triglycerides and cholesterol has been difficult in commonly used non-mammalian models such as worms and flies. Chu et al. now report a transgenic zebrafish model of obesity overexpressing a constitutively active form of human AKT1. AKT is a kinase that functions in multiple cellular processes, including adipogenesis, and is central to the insulin signalling pathway. The zebrafish that was developed expresses AKT1 under the control of a skin-specific promoter, but the transgene is also expressed in several pre-adipocyte cell types, possibly owing to integration-positional effects. Compared with control fish, adult AKT1-transgenic zebrafish were larger and had enhanced adipogenesis, increased lipid content, and upregulated expression of adipokines and inflammatory markers. Moreover, they had elevated blood triglycerides and glucose intolerance, which are early indicators of metabolic syndrome. These results introduce AKT1-transgenic zebrafish as a powerful model for high-throughput screening for anti-obesity drugs.
Chu C. Y., Chen C. F., Rajendran R. S., Shen C. N., Chen T. H., Yen C. C., Chuang C. K., Lin D. S., Hsiao C. D. (2012). Overexpression of Akt1 enhances adipogenesis and leads to lipoma formation in zebrafish. PLoS ONE 7, e36474.
