A team led by researchers at Georgia State University has identified a novel group of neurons controlling the brain-heart-gut axis which can be activated to induce a hypometabolic state that resembles hibernation. The discovery could have wide-ranging impacts for scientific fields ranging from obesity to cardiometabolic health, and even space travel.
The new study is published in the journal Nature Metabolism.
Lead author Eric Krause is a professor of neuroscience, a Georgia Research Alliance (GRA) Distinguished Investigator at Georgia State University and a core member of the Center for Neuroinflammation and Cardiometabolic Disease (CNCD). Krause worked with researchers from the University of Florida and the Monell Chemical Senses Center in Philadelphia.
“We identified this population of neurons located near the base of the skull that relay the sensation of mechanical stretch exerted on the gut and heart to the brain. When these neurons are activated, they seem to recreate the sensation of feeling full or having increased blood pressure,” Krause said. “We found that activating these neurons suppresses eating and lowers blood pressure, heart rate and whole-body metabolism.”
During the research, the team discovered that simultaneous, recurrent firing of these neurons in mice produces a torpor-like state, similar to that of animals in hibernation, characterized by reductions in cardiac output, body temperature and energy expenditure.
“We found that repeated excitation of the neurons decreased body mass and produced a hypometabolic state without inducing anxiety-like behaviors that are often observed with chronic stress,” Krause said. “This is changing what we know about body-to-brain communication and how profoundly it affects physiology and behavior.”
The researchers were able to activate the population of neurons through a process known as chemogenetic excitation. Utilizing animal models to manipulate oxytocin signaling in the vagal sensory neurons, the team was able to assess impacts on various sensory function.
Oxytocin is commonly known as the love hormone and regulates how we respond to other people. Krause said the findings indicate that oxytocin may act on these neurons to also rule how we feel about ourselves, similar to what we think of as “gut feelings” or “heartache.”
Krause said activating these neurons could be leveraged therapeutically to achieve weight loss without prolonged hypometabolism or stress side effects.
Researchers also believe this discovery could be a step toward developing treatments for cardiometabolic disease and extending longevity. Torpor is also being explored for applications ranging from biomedical therapeutics to slowing the metabolic rate of astronauts to enable long-duration space travel.
Guillaume de Lartigue is a co-author on the study and a researcher with the Monell Chemical Senses Center. He called this discovery an exciting step toward unlocking the therapeutic potential of the vagus nerve.
“We’ve tapped into the body’s own energy-saving toolkit. By activating these neurons, we can trigger an ancient survival mechanism present in mammals,” de Lartigue said. “If we can control the body’s on/off switch for energy use, the implications for human health are extraordinary.”
Annette de Kloet, an associate professor of neuroscience and part of the Georgia State research team, said the research highlights a novel approach to decreasing food intake, body weight and blood pressure without negative anxiogenic consequences.
“This discovery may lead to novel approaches that take advantage of body-brain communication to alleviate stress-induced cardiometabolic diseases, like obesity and hypertension,” de Kloet said.
The research team has recently been awarded an additional $3.4 million grant from the National Institutes of Health to continue its work.
“Our GRA Distinguished Investigators are recognized for their exceptional vision and expertise,” said Donald Hamelberg, interim vice president for research and economic development at Georgia State. “This latest breakthrough highlights the research excellence these scholars contribute to our university and to society.”
