Obesity affects over a third of the global population and is a major risk factor for numerous chronic diseases. To find better therapies to fight obesity and its related health problems, researchers at Northwell Health’s Feinstein Institutes for Medical Research are investigating a promising new approach in which vagus nerve stimulation (VNS) interacts with growth factor-β (TGF-β) signaling, a driver and suppressor of metabolic function.

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Dr. Lopa Mishra led the research. (Credit: Feinstein Institutes).

Published today in Bioelectronic Medicine – an open-access journal published by the Feinstein Institutes and BMC, part of Springer Nature – and led by Lopa Mishra, MD, co-director and professor in the Institute of Bioelectronic Medicine at the Feinstein Institutes, the review shows growing evidence that stimulating the vagus nerve could offer a much-needed non-drug treatment for obesity. The review provides valuable insights into the complex processes in obesity and related illnesses, specifically looking at TGF-β signaling, which acts as a contributer to metabolic problems and other times helps to regulate them.

The vagus nerve connects the brain to the stomach and other organs. Researchers are now investigating how VNS might interact with TGF-β signaling, potentially fine-tuning its effects to improve metabolic health, while also focusing on the SPTBN1 protein, which acts as a switch for the TGF-β system and may be a promising drug target.

“This research is our response to the urgent need for innovative strategies that combat the global obesity epidemic and its devastating consequences,” said Dr. Mishra. “By elucidating the intricate interplay between TGF-β signaling, vagus nerve stimulation and metabolic dysfunction, there’s potential to identify more precise and effective therapeutic targets.”

Obesity significantly increases the risk of developing several serious diseases, including fatty liver disease, liver damage and liver cancer. Current drug treatments often face limitations, including lack of effectiveness for some individuals, high discontinuation rates due to side effects, and the potential for weight regain after stopping the medication. VNS offers a potential alternative or complementary approach, especially given recent advancements in non-invasive ultrasound stimulation techniques by delivering small, safe electrical pulses to the vagus nerve. Researchers believe they can help people feel fuller faster, leading to reduced food intake and weight loss as the vagus nerve plays a critical role in the signaling the feeling of fullness.

“Dr. Mishra and her team's research on TGF-β and vagus nerve stimulation provides an interesting new insight into the mechanisms of obesity,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research. “These are novel pathways and targets that may one day lead to new therapies.”

The Feinstein Institutes for Medical Research is the global scientific home of bioelectronic medicine, which combines molecular medicine, neuroscience and biomedical engineering. At the Feinstein Institutes, medical researchers use modern technology to develop new device-based therapies to treat disease and injury.

Building on years of research in molecular disease mechanisms and the link between the nervous and immune systems, Feinstein Institutes’ researchers discovered neural targets that can be activated or inhibited with neuromodulation devices, like vagus nerve implants, to control the body's immune response and inflammation. If inflammation is successfully controlled, diseases – such as arthritis, pulmonary hypertension, heart failure, inflammatory bowel diseases, diabetes, cancer and autoimmune diseases – can be treated more effectively.

Beyond inflammation, using novel brain-computer interfaces, Feinstein Institutes' researchers developed techniques to bypass injuries of the nervous system so that people living with paralysis can regain sensation and use their limbs. By producing bioelectronic medicine knowledge, disease and injury could one day be treated with our own nerves without costly and potentially harmful pharmaceuticals.

About the Feinstein Institutes

The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State. Encompassing 50+ research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its six institutes of behavioral science, bioelectronic medicine, cancer, health system science, molecular medicine, and translational research. We are the global scientific leader in bioelectronic medicine – an innovative field of science that has the potential to revolutionize medicine. The Feinstein Institutes publishes two open-access, international peer-reviewed journals Molecular Medicine and Bioelectronic Medicine. Through the Elmezzi Graduate School of Molecular Medicine, we offer an accelerated PhD program. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

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