The Hungry Brain: Outsmarting the Instincts That Make Us Overeat

by Stephan Guyenet

What emerged from these studies was a remarkably logical explanation for how leptin regulates the lipostat: It turns off neurons that drive eating, and it turns on neurons that inhibit eating. And, by implication, when leptin levels decline, neurons that drive eating turn on and neurons that inhibit eating turn off, increasing the drive to eat. This “push-pull” system is redundant and extremely robust, and only disrupting major nodes in the signaling pathway can derail it. Disrupting a major node is precisely what Albert Hetherington and Stephen Ranson did by damaging the VMN “satiety center” in the rat studies we encountered early in the last chapter. The VMN contains neurons that stimulate POMC neurons, and when it’s destroyed, POMC neurons become less active and cease to restrain appetite. As Hetherington and Ranson showed, this makes rats overeat tremendously and grow to impressive proportions. But it doesn’t require brain damage to disrupt a major node in the signaling pathway. Getting rid of leptin is another way to do so, and as we’ve seen, the result is the same.