Summary: Researchers report on the role the arcuate nucleus plays in metabolic regulation and appetite suppression following exercise.
Source: Albert Einstein College of Medicine.
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.
About this neuroscience research article
Funding: James Kesby receives funding from the Queensland Government from an Advance Queensland Research Fellowship and from the National Health and Medical Research Council.
Source: Deirdre Branley – Albert Einstein College of Medicine Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Open access research for “Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake” by Jae Hoon Jeong, Dong Kun Lee, Shun-Mei Liu, Streamson C. Chua Jr., Gary J. Schwartz, and Young-Hwan Jo in PLOS Biology. Published April 24 2018. doi:10.1371/journal.pbio.2004399
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[cbtabs][cbtab title=”MLA”]Albert Einstein College of Medicine “Link Between Exercise and Appetite Loss Explained.” NeuroscienceNews. NeuroscienceNews, 28 April 2018. <https://neurosciencenews.com/exercise-appetite-loss-8910/>.[/cbtab][cbtab title=”APA”]Albert Einstein College of Medicine (2018, April 28). Link Between Exercise and Appetite Loss Explained. NeuroscienceNews. Retrieved April 28, 2018 from https://neurosciencenews.com/exercise-appetite-loss-8910/[/cbtab][cbtab title=”Chicago”]Albert Einstein College of Medicine “Link Between Exercise and Appetite Loss Explained.” https://neurosciencenews.com/exercise-appetite-loss-8910/ (accessed April 28, 2018).[/cbtab][/cbtabs]
Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake
Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1)-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR), immunohistochemistry, electrophysiology, TRPV1 knock-out (KO), and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5) carrying a Cre-dependent channelrhodopsin-2 (ChR2)–enhanced yellow fluorescent protein (eYFP) expression cassette under the control of the two neuronal POMC enhancers (nPEs). Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.