Healthcare (Commonwealth Union) – Scientists have long known that the stomach communicates with the brain, but new research from Rutgers Health suggests it’s less a polite exchange and more a battle for control—one side pushing for more food, the other calling it quits.
Two studies, published in Nature Metabolism and Nature Communications, together map out the brain’s first integrated circuit diagram for hunger and fullness. Their findings could help fine-tune today’s popular weight-loss medications while reducing unwanted side effects.
In one study, Zhiping Pang of the Center for NeuroMetabolism at the Robert Wood Johnson Medical School identified a narrow network of neurons linking the hypothalamus to the brainstem.
These nerve cells are rich in GLP-1 receptors—the same type activated by weight-loss drugs like Ozempic. When Pang’s team stimulated the pathway with light pulses, mice that had already eaten stopped eating. But when the pathway was suppressed or the receptors removed, the mice gained weight. Notably, fasting weakened this circuit until natural or synthetic GLP-1 was introduced, which reactivated it.
Pang described the synapse as acting like a volume control that only increases when the body’s energy reserves are low. He cautioned that medications which keep this signal elevated continuously could interfere with the brain’s natural cycles, potentially causing some of the known side effects of GLP-1 drugs—such as nausea, vomiting, constipation, diarrhea, and muscle loss.
In the other study, Mark Rossi—who co-directs the Center for NeuroMetabolism alongside Pang—mapped the neural pathway responsible for initiating hunger. His team followed inhibitory neurons from the stria terminalis to similar neurons in the lateral hypothalamus.
When researchers activated this pathway, mice that had not previously shown interest quickly rushed to drink sugar water. When the circuit was inhibited, even mice that hadn’t eaten in a while remained inactive and showed little interest in food.
Researchers of the study pointed out that hormones influenced the outcome. A dose of ghrelin—the gut hormone that signals hunger—intensified the drive to seek food, whereas leptin—the hormone that signals fullness—quickly suppressed it. Mice that were overfed gradually stopped responding to these cues, but the sensitivity came back once they lost weight through dieting.
“Pang’s pathway shuts things down,” says Rossi. “Ours steps on the accelerator.”
Though the neural circuits are located in separate regions of the brain, both research teams observed the same core dynamic: the body’s energy status rapidly reshapes synaptic connections. When fasting, the hunger pathway becomes more responsive, while the satiety circuit becomes less active; after eating, the pattern reverses.
This marks the first time scientists have observed this push-and-pull effect operating in parallel neural networks—a yin-yang balance that may shed light on why diets and treatments that address only one side of the equation tend to lose effectiveness over time. The discovery could aid in developing more advanced therapies beyond current GLP-1-based drugs.
Researchers of the study indicated that GLP-1 analogs like Wegovy and Zepbound can produce significant weight loss, but often come with side effects like nausea, diarrhea, and even muscle loss. Pang’s findings suggest that treatments aimed specifically at brainstem pathways—without affecting peripheral organs—might reduce appetite with fewer adverse effects. Meanwhile, Rossi’s research indicates that helping the body regain sensitivity to the hunger hormone ghrelin could benefit people who stop losing weight after extended calorie restriction.
Both teams plan to pursue follow-up studies to answer key questions that could lead to better drug development. Pang aims to monitor GLP-1 release in real time to determine if brief pulses—rather than sustained exposure—are sufficient to suppress appetite. Meanwhile, Rossi is working to identify the molecular profile of the neurons that drive hunger, with the goal of discovering drug targets that can curb cravings without eliminating the pleasure of eating.
“You want to keep the system’s flexibility,” explained Rossi. “It’s the difference between dimming the lights and flicking them off.”
