Intracellular fat signals

Leptin is an adipocyte-derived hormone that promotes weight loss and has recently been shown to be important in blood vessel growth, control of reproduction, and immunity. Leptin communicates with cells through a membrane receptor (LRb), but the identity of the precise intracellular signaling pathways involved has been unclear. In the February 20 Nature, Sarah H. Bates and colleagues at the Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA, show that leptin signaling through STAT3 transcription factor is important for regulation of energy balance but not reproduction (Nature, 421:856-859, February 20, 2003).

Bates et al. engineered mice homozygous for a leptin receptor with a serine residue (LRbS1138) that fails to activate STAT3, although it mediates other leptin signals normally. They observed that leprS1138 homozygotes (s/s) are hyperphagic and obese, but are still fertile, long and less hyperglycaemic. This was in contrast to db/db mice that lack completely LRb and ...