April 24, 2018--(BRONX, NY)--Ever wonder why intense exercise temporarily curbs your appetite? In research described in today's issue of PLOS Biology, Albert Einstein College of Medicine researchers reveal that the answer is all in your head--more specifically, your arcuate nucleus.
Senior author Young-Hwan Jo, Ph.D., associate professor of medicine and of molecular pharmacology at Einstein, runs on a track near his house three times a week for 30 to 45 minutes at a time. Like many exercisers, he noticed two things about intense workouts: they raised his body temperature and reduced his appetite for several hours afterward.
"I'm a neuroscientist who studies the hypothalamus--the portion of the brain that plays the central role in regulating metabolism and weight," he says. "I wondered if certain hypothalamic neurons sense temperature increases and respond to exercise-induced warming by releasing a 'stop eating!' message."
Anyone who's suffered a burn or eaten a jalapeño pepper knows that sensory neurons with "heat-detecting" receptors (called TRPV1 receptors) abound in the body. Those neurons react to physical heat and to capsaicin, the active ingredient in jalapeños and many other spicy foods. Could brain neurons possess similar receptors?
Dr. Jo focused on appetite-suppressing proopiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the hypothalamus. Some of those neurons are not shielded by the blood-brain barrier, so they're able to directly detect and respond to hormones and nutrients in the blood. He wondered whether those neurons sense changes in body temperature as well.
To sense and respond to heat, ARC POMC neurons would need receptors similar to the capsaicin- and heat-sensitive TRPV1 receptors found elsewhere in the body. Dr. Jo and colleagues took mouse hypothalamus tissue containing POMC neurons and exposed the tissue to capsaicin or to heat, to see if such receptors were present.
Sure enough, both capsaicin and heat caused POMC neurons to fire by activating their receptors. About two-thirds of the ARC's POMC neurons possessed such receptors. Next came experiments exploring the role of POMC neurons and their TRPV1 receptors in reducing appetite and curbing food intake. Dr. Jo and colleagues found that:
- Infusing capsaicin into the ARC of mice reduced the amount of food they ate over the next 12 hours. Researchers could prevent this appetite suppression by first blocking the POMC neurons' TRPV1-like receptors or silencing the gene that codes for those receptors.
- When mice were put on treadmills for 40 minutes, their body and ARC temperatures rapidly increased, plateauing after 20 minutes and remaining at that elevated level for more than an hour. After the workout, the mice reduced their food intake by about 50 percent compared with non-exercising mice.
- Bouts of treadmill exercise did not affect the food intake of mice whose ARC POMC neurons lacked TRPV1 receptors.
"Our study provides evidence that body temperature can act as a biological signal that regulates feeding behavior, just like hormones and nutrients do," says Dr. Jo. He also notes that his findings could lead to new approaches for suppressing appetite or helping people lose weight.
The PLOS Biology paper is titled "Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake." The other authors, all from Einstein, were Jae Hoon Jeong, Ph.D., Dong Kun Lee, Ph.D., Shun-Mei Liu, M.D., Streamson Chua, M.D., Ph.D., and Gary Schwartz, Ph.D.
About Albert Einstein College of Medicine
Albert Einstein College of Medicine, part of Montefiore, is one of the nation’s premier centers for research, medical education and clinical investigation. During the 2017-2018 academic year, Einstein is home to 697 M.D. students, 181 Ph.D. students, 108 students in the combined M.D./Ph.D. program, and 265 postdoctoral research fellows postdoctoral research fellows. The College of Medicine has more than 1,900 full-time faculty members located on the main campus and at its clinical affiliates. In 2017, Einstein received more than $174 million in awards from the National Institutes of Health (NIH). This includes the funding of major research centers at Einstein in aging, intellectual development disorders, diabetes, cancer, clinical and translational research, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Its partnership with Montefiore, the University Hospital and academic medical center for Einstein, advances clinical and translational research to accelerate the pace at which new discoveries become the treatments and therapies that benefit patients. Einstein runs one of the largest residency and fellowship training programs in the medical and dental professions in the United States through Montefiore and an affiliation network involving hospitals and medical centers in the Bronx, Brooklyn and on Long Island. For more information, please visit www.einstein.yu.edu, read our blog, follow us on Twitter, like us on Facebook and view us on YouTube.