From Flies to Mice: Drosophila as a Model System to Study Fat Biology

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Title: From Flies to Mice: Drosophila as a Model System to Study Fat Biology
Author: Suh, Jaemyoung
Abstract: Adipose tissues are found in a wide range of animal species ranging from invertebrates to mammals and are essential for many aspects of the animal life cycle . Fat biology has taken on a new and urgent importance as it is intimately linked to one of the most prevelant and costly health problems of our time - obesity . Model organisms are a powerful resource for the discovery of genes critical to human health and disease . Thus far , the utility of Drosophila melanogaster as a model system to study fat biology has not been critically evaluated . My studies highlight the potential of this system to uncover new genes and pathways that may impact our current understanding of adipose biology . Hedgehog signals regulate invertebrate and vertebrate development , yet the role of the cascade in adipose development was undefined . I found that fat body specific transgenic activation of Hedgehog signaling inhibited fly fat formation . Conversely , fat body specific Hedgehog blockade stimulated fly fat formation . Strikingly , the anti -adipogenic effect of Hedgehog signaling was conserved in mammalian adipogenic models in both sufficiency and necessity tests . Hedgehog signals elicit this function early in adipogenesis , upstream of PPARgamma , potentially acting as a molecular switch diverting preadipocytes and mesenchymal prescursors away from adipogenesis and towards osteogenesis . In another study , I investigated the role of Adipose , an evolutionarily conserved gene isolated from naturally occurring obese flies . Through gain - and loss -of -function studies in flies , mammalian cell culture , and mice I showed that the Adipose pathway plays a conserved role in obesity and diabetes . Furthermore , I found that Adipose controls the activity of PPARgamma , a central regulator of adipogenesis and the target of the thiazolidinedione class of anti -diabetic drugs . Adipose inhibits PPARgamma function by directly binding Med23 , a component of the Mediator Complex , which connects transcription factors with RNA polymerase II . Taken together , I have shown that both the Hh and Adp pathway have evolutionary conserved functions in fat formation . These results support the idea that Drosophila is a useful system to study adipose biology and discoveries in flies will lead to biological insights relevant to mammals and the treatment of obesity and diabetes .
URI: http : / /hdl .handle .net /2152 .5 /221
Date: 2006-12-20

Citation

From Flies to Mice: Drosophila as a Model System to Study Fat Biology. Graduate School of Biomedical Sciences. Available electronically from http : / /hdl .handle .net /2152 .5 /221 .

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