The diabetes drug rosiglitazone improves insulin sensitivity by acting not only on fat and muscle cells, but also on the brain.

Rosiglitazone binds to a protein receptor called PPAR-γ, which regulates lipid and glucose metabolism. One side effect, however, is weight gain. Randy Seeley and his colleagues at the University of Cincinnati in Ohio found that the drug activates PPAR-γ in the rat central nervous system. Administering rosiglitazone directly to the brain, or overexpressing PPAR-γ in a brain region called the hypothalamus, boosted the rats' appetite and weight gain.

Meanwhile, Jerrold Olefsky at the University of California, San Diego, Michael Schwartz at the University of Washington in Seattle and their colleagues found that mice lacking PPAR-γ in neurons ate less food and used more energy than normal mice. But rosiglitazone didn't work in these mice — it seems that active neuronal PPAR-γ is required for the drug's insulin-sensitizing effects.

Nature Med. doi:10.1038/nm.2349 (2011); Nature Med. doi:10.1038/nm.2332 (2011)