Metabolic disorders such as obesity and type 2 diabetes are challenging to treat owing to the complex regulatory mechanisms that maintain energy balance. Efforts to identify drugs that target fat accumulation have found many compounds that show high efficacy in cell culture systems but have limited success when tested in whole animals. Lemieux et al. now report a new in vivo strategy using C. elegans, and screened 3200 small molecules to find regulators of fat storage. They discovered several compounds that either increased or decreased fat content without affecting feeding, growth or reproduction. A subset of these compounds was also found to regulate fat storage in mammalian and insect cell lines. Notably, one compound reduced fat accumulation via a transcription factor with no previously described role in metabolism. These data demonstrate a cost-effective and high-throughput in vivo screen for small molecules that regulate fat storage, with advantages over existing cell-based assays.

Lemieux G. A., Liu J., Mayer N., Bainton R. J., Ashrafi K., Werb Z. (2011). A whole-organism screen identifies new regulators of fat storage. Nat. Chem. Biol. 7, 206213.

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