Mapping obesity circuitry in brain

In the battle of the bulge, one important battalion is a set of brain cells expressing the melanocortin-4 receptor (MC4R). Via signals from the fat-derived hormone leptin, these neurons regulate feeding behavior and fat metabolism in an attempt to regulate body weight. But how leptin influences and acts on this brain circuitry is not fully understood.

Using mice with fluorescently-tagged MC4R, Masoud Ghamari-Langroudi, Roger Cone and colleagues analyzed how the activity of MC4R neurons of the paraventricular nucleus of the hypothalamus (PVN) are regulated by leptin and by metabolic state (i.e., fasting).

They report in the Jan. 4 Proceedings of the National Academy of Sciences that fasting increases firing of these neurons and that leptin administration returns the firing to normal levels. They also show that contrary to the conventional view that leptin indirectly regulates PVN neuron activity, it can also inhibit the activity of PVN neurons directly. Such details of the brain circuitry underlying energy balance could provide important clues to understanding – and combating – obesity.