Scientists know the stomach talks to the brain, but two new studies from Rutgers Health researchers suggest the conversation is really a tug-of-war, with one side urging another bite, the other signaling “enough.” Together, the papers in Nature Metabolism and Nature Communications trace the first complementary wiring diagram of hunger and satiety in ways that could refine today’s blockbuster weight-loss drugs and blunt their side effects.
One study, led by Zhiping Pang of Robert Wood Johnson Medical School’s Center for NeuroMetabolism, pinpointed a slender bundle of neurons that runs from the hypothalamus to the brainstem. The cells bristle with GLP-1 receptors, the proteins mimicked by weight-loss drugs such as Ozempic. When Pang’s team hit the pathway with pulses of light, well-fed mice quit eating; when they silenced the circuit or deleted the receptor, the animals packed on weight. Fasting weakened the connection until a burst of natural or synthetic GLP-1 restored it.
“The synapse is a volume knob that only turns up when energy stores are low,” Pang said, warning that drugs that keep the signal high around the clock could disrupt the brain’s normal rhythm and create some of the side effects of GLP-1 drugs such as nausea, vomiting, constipation or diarrhea and muscle wasting. For the other paper, Mark Rossi, who co-leads the Center for NeuroMetabolism with Pang, charted the circuit that triggers hunger. His group traced inhibitory neurons in the stria terminalis to similar cells in the lateral hypothalamus. To read the full story.