The Center for NeuroMetabolism set to become a leader in metabolic health research

Rutgers Health has launched the Center for NeuroMetabolism to advance the understanding of how the brain and body interact to regulate metabolic health, with a focus on disorders such as type 2 diabetes, obesity, and gastrointestinal, vascular, and inflammatory conditions.

As part of the Child Health Institute of New Jersey and Rutgers Robert Wood Johnson Medical School (RWJMS), the center strives to become a global leader in metabolic health research and hasten the development of targeted drug therapies with fewer side effects.

“The Center for NeuroMetabolism is a beacon of scientific excellence, attracting world-class talent and fostering an environment that inspires groundbreaking discoveries, strengthens community ties, and propels Rutgers to the forefront of global neurometabolism research,” said Amy P. Murtha, MD, dean of Robert Wood Johnson Medical School.

For decades, scientists have sought to understand how the brain monitors internal energy states and uses that information to influence behavior.

Research indicates that regulatory systems in the brain and body, including the gastrointestinal, vascular, and immune systems, play a critical role in shaping eating behaviors and metabolic function.

“Metabolic disease is not like a cancer or a traumatic brain injury that will kill you quickly, but it is a disease that will cause a lot of health issues that will affect daily life and cause long-term health problems,” said Zhiping Pang, director of the Center for NeuroMetabolism, Henry Rutgers Professor in the Department of Neuroscience and Cell Biology, and a resident member of the Child Health Institute of New Jersey.

Pang is working with the center’s founding member Mark Rossi, a neuroscientist and assistant professor in the Department of Neuroscience and Cell Biology.

Brain Rewires Itself Based on Energy Status 

The two scientists want to know what triggers hunger and how to calm appetite without destroying the joy of eating.
In recently published findings in Nature Metabolism and Nature Communications, their research indicates that there is a tug-of-war going on between the brain and the gut as to when to continue eating and when enough is enough and it’s time to stop.

Pang and Rossi discovered two complementary brain pathways that adjust in real time based on the body’s actual energy needs. Their studies reveal how these circuits adapt and how this process breaks down during obesity.

Pang’s laboratory identified neurons running from the hypothalamus, a part of the brain that helps regulate hunger. These cells are packed with GLP-1 receptors, the same proteins that are targeted by weight-loss drugs like Ozempic and Wegovy.

When this pathway was activated in mice, they ate less. But when the pathway was disrupted by removing the GLP-1 receptors or silencing the circuit, the mice began overeating and gained weight.

The team also showed that the brain circuit changes based on how much energy the body needs. It responds strongly to GLP-1 during hunger and much less after eating. After twelve weeks on a high-fat diet, the brain stopped  identifying hunger from fullness.

Rossi’s team mapped an opposing circuit that triggers hunger, focusing on a small area in the brain that turns affective state and motivation into actions. 

The team showed that turning on part of the brain involved in stress, emotions, motivation, and hunger can increase the drive to seek out food, especially when the body needs energy.

The response got stronger when animals were hungry and weaker after eating. While eating unhealthy food dulled this sensitivity, reverting to lower-calorie food restored it. What this means, the researchers say, is that there is a specific brain circuit that helps control appetite, and it works through the same system as some major weight-loss drugs.

“Pang’s pathway shuts things down,” Rossi said. “Ours steps on the accelerator.” These findings are critical for millions of people throughout the United States for which dieting alone hasn’t been effective when it comes to long-term weight loss. While drugs such as Ozempic, Wegovy, and Mounjaro that regulate blood sugar, appetite, and digestion promote weight loss by acting like naturally occurring hormones and sending a signal to the brain that the person is full, they can also cause nausea, diarrhea, and, in some cases, muscle loss.

The new research showing that the brain has a flexible, self-adjusting system for managing hunger and recovering even after being thrown off balance by overeating could lead to the development of weight-loss treatments that help the brain naturally manage hunger throughout the day, instead of using drugs that constantly turn off appetite.

Arnold Rabson, director of the Child Health Institute of New Jersey and professor of pharmacology, pediatrics and pathology and laboratory medicine at the medical school, said the worldwide epidemic of obesity and metabolic syndrome that has created incredible health-related concerns and overwhelmed health care costs is one of the main reasons behind developing the Center for NeuroMetabolism.

“It is imperative that there be substantial and focused research that takes into account all the different factors that contribute to the obesity epidemic and the chronic health problems it causes,” Rabson said.

Big Picture

Over the next few years, Pang and Rossi will be joined by six additional principal investigators, adding to the team of senior-level leaders, physician scientists, postdoctoral fellows, and graduate, medical, and undergraduate trainees who work side by side with New Jersey translational research centers and biotech companies as well as Nokia Bell Laboratories.

These partnerships will provide an ideal environment for complex studies and translational research, Pang said, creating collaborations with scientists in neuroscience, endocrinology, genetics, behavioral science, nutrition, pharmacology, neuroimaging, and clinical research at RWJMS and Rutgers Brain Health Institute.

“Our mission is to discover basic metabolic and neural mechanisms and integrated regulatory pathways, and to translate these breakthroughs into transformative clinical therapeutics,” Pang said. “We are confident that Rutgers is uniquely positioned to leverage various departments and resources that will help to bridge the gap between research and clinical practice and better understand the brain-body connection.”