Nature Neuroscience pp 227 - 233

The level of a simple substance in a small brain region may act as a crucial signal in the regulation of body weight, reports a study in the February issue of Nature Neuroscience.

Complex cross-talk between the brain and the gut regulates food consumption and body weight. The primary regulators of eating and weight gain or loss in the brain are a group of nerve cells in the hypothalamus. High levels of fatty acids in this brain region have been reported to act as a signal to stop eating. In the new study, Luciano Rossetti and colleagues used a virus vector to reduce levels of malonyl-CoA in this part of the hypothalamus. malonyl-CoA inhibits the breakdown of fatty acids into energy, so reducing malonyl-CoA resulted in chronically low levels of fatty acids. This caused the animals to overeat, apparently by resetting the finely balanced nutrient sensor in the brain.

These results suggest that elevating levels of malonyl CoA in the hypothalamus might be beneficial in the treatment of overweight patients. The enzymes that produce malonyl-CoA might therefore be promising targets for anti-obesity drugs.

Nature Neuroscience pp 220 - 226

Differences between male and female brains develop through a complex train of events involving actions of the hormone estrogen in the fetal brain. A protein called alpha-fetoprotein (AFP) binds to and regulates gender-determining estrogen during fetal development, but its exact function has remained unclear. Now, Julie Bakker and colleagues answer this longstanding question in the February 2006 issue of Nature Neuroscience.

In male fetuses, testosterone produced in the testes is converted to estrogen, which powerfully influences protein expression in the developing male brain. Female fetuses produce no testosterone and have much lower levels of brain estrogen, mostly derived from the mother_s ovaries. It was unknown whether AFP works to transport the little available estrogen into the brain for efficient use or to prevent estrogen_s _masculinizing_ influence by binding to it and keeping it out of the brain. The authors found that female mice without the AFP gene behaved more like males as adults, and that certain structures in their brains were masculinized. When the authors blocked estrogen production in pregnant mice bearing fetuses without AFP _ so that female fetuses had no circulating estrogen at all _ mice grew up to behave like normal females. These results suggest that, in normal female fetuses, AFP acts to keep estrogen out of the developing brain. Paradoxically, this hormone, which is normally associated with females, promotes masculine brain development during the prenatal period, and AFP protects female brains from its influence. The new findings help to explain why female fetuses are not masculinized by hormones coming from their male neighbors in the womb.