After a long, tough workout, it would seem people should be ravenous. They’ve been working hard and burning calories — energy that must be replaced by fueling the body with more food. So why do most people and animals eat less after exercise? Scientists think they’ve found the answer in certain brain cells that control appetite. When they get hot and bothered, those cells appear to shut down the need to feed.
Young-Hwan Jo is a neuroscientist — someone who studies the brain. He works at Albert Einstein College of Medicine in New York City. And as an athlete, Jo admits he has a personal stake in studying exercise and appetite. “I run three times a week,” he notes, and afterward “I’m not very hungry.” Being a scientist, he wanted to know why these workouts suppressed his appetite.
As Jo thought about the role of exercise, heat kept coming to mind. “Exercise increases body temperature,” he explains. Maybe the brain was responding to warmer temperatures by reducing hunger. Jo and his team decided to test that idea. They focused on the brain’s hypothalamus because it is important in controlling appetite. Located near the center of the brain, it’s roughly behind the bridge of your nose. This tissue releases hormones — chemicals that travel in blood to reach even distant parts of the body.
The hypothalamus isn’t just one big glop of cells. Within it, small groups of nerve cells, or neurons — known as nuclei — perform different functions. One group of cells, the arcuate (AR-kew-ate) nucleus, is important in controlling appetite.
A complex layer of cells, known as the blood-brain barrier, serves to protect the brain from potential poisons that might be circulating in the blood. In the process, the blood-brain barrier also protects the brain from heat in the bloodstream. But some brain cells dangle outside this protective barrier, notes Jo — including cells in the arcuate nucleus.
Those dangling cells might sit in the right place to sense temperature and respond to the tiny fever that animals get when they exercise, he reasoned. Jo’s team would go on to show this was true. And in the April 28 PLOS Biology, they linked this heat response to appetite.
Heating it up
In mice, Jo’s team showed, brain cells in the arcuate nucleus respond to a chemical called capsaicin (Kap-SAY-sin). It’s the same molecule that gives spicy chilis their heat. Capsaicin delivers that heat by binding to a receptor — a molecule on the outside of cells that serves as a docking station. Known as the TRPV1 receptor, this molecule can sense temperature. Cells in the arcuate nucleus host plenty of TRPV1 receptors. Jo suspected that these might respond to the tiny fever animals get when they exercise.
To test their role in appetite, Jo’s team put some capsaicin in the arcuate nucleus of male and female mice. It docked with the TRPV1 receptors there and the mice ate less. Jo and his colleagues then blocked these receptors in the brains of the mice. Now, their brain cells didn’t respond to the capsaicin — and the animals ate normally.
The researchers then had their mice get in shape. They trained the animals to run on treadmills for 40 minutes at a time. After each workout, the body temperature climbed in these mice — including in their brains’ arcuate nucleus. The rodents also ate less.
As a final test of the role of those TRPV1 receptors, the scientists bred a knockout mouse. Brain cells in these animals lacked the instructions for making TRPV1 receptors. When these mice ran on the treadmills, their body temperatures went up, including in their brains’ arcuate nucleus. But this exercise-induced fever didn’t affect their appetite. These mice ate just as much as they had before exercising.
“People know that after they exercise they lose their appetite,” Jo observes. “This could be one of the mechanisms.” His team can’t say it’s the only mechanism, though. Jo admits that when it comes to the answer, TRPV1 “could be just a part.”
“It’s interesting to understand the mechanism of why, when you stop exercising, you’re not hungry,” says Alissa Nolden. She’s a food scientist at the Monell Chemical Senses Center in Philadelphia, Pa. “It’s cool you can get this kind of information [in mice] that you couldn’t get in a human,” she adds. Nolden works with people. And she knows that “injecting capsaicin into the brain [of a person] wouldn’t go over well.”
Still, Nolden cautions that receptors can change over time when they are stimulated repeatedly. If exposed to hot blood from exercise over and over and over, she says, the TRPV1 receptors might become less sensitive. Then, no matter how hot she got, an athlete might still be ravenous after her race. That’s why Nolden suspects it will take more science — and possibly more mice on treadmills — to know for sure.
arcuate nucleus A collection of cells in the brain’s hypothalamus that play a pivotal role in regulating hunger. This region responds to signals it gets from the brainstem and from spot elsewhere throughout the body.
biology The study of living things. The scientists who study them are known as biologists.
blood-brain barrier A barrier of tightly packed cells that carefully regulate what molecules can — and can’t — enter the brain. The barrier protects the brain from foreign substances in the blood and helps to maintain a constant environment for brain cells.
calorie The amount of energy needed to raise the temperature of 1 gram of water by 1 degree Celsius. It is typically used as a measurement of the energy contained in some defined amount of food.
capsaicin The compound in spicy chili peppers that imparts a burning sensation on the tongue or skin.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
colleague Someone who works with another; a co-worker or team member.
docking The act of bringing together and inserting one thing into another.
hormone (in zoology and medicine) A chemical produced in a gland and then carried in the bloodstream to another part of the body. Hormones control many important body activities, such as growth. Hormones act by triggering or regulating chemical reactions in the body.
hypothalamus A region of the brain that controls bodily functions by releasing hormones. The hypothalamus is involved in regulating appetite through release of appetite-suppressing hormones.
knockout (in genetics) The term for an organism that has been bred or engineered in such a way that one of its genes has been disabled, or turned off. The term gets its name from the fact that the function of this gene has been knocked out by the procedure. Scientists can now identify the function of the missing gene by seeing how a cell — or organism — differs when this gene no longer works.
mechanism The steps or process by which something happens or “works.” It may be the spring that pops something from one hole into another. It could be the squeezing of the heart muscle that pumps blood throughout the body. It could be the friction (with the road and air) that slows down the speed of a coasting car. Researchers often look for the mechanism behind actions and reactions to understand how something functions.
molecule An electrically neutral group of atoms that represents the smallest possible amount of a chemical compound. Molecules can be made of single types of atoms or of different types. For example, the oxygen in the air is made of two oxygen atoms (O2), but water is made of two hydrogen atoms and one oxygen atom (H2O).
nerve A long, delicate fiber that transmits signals across the body of an animal. An animal’s backbone contains many nerves, some of which control the movement of its legs or fins, and some of which convey sensations such as hot, cold or pain.
neuron An impulse-conducting cell. Such cells are found in the brain, spinal column and nervous system.
neuroscientist Someone who studies the structure or function of the brain and other parts of the nervous system.
ravenous Adjective meaning exceptionally hungry.
receptor (in biology) A molecule in cells that serves as a docking station for another molecule. That second molecule can turn on some special activity by the cell.
rodent A mammal of the order Rodentia, a group that includes mice, rats, squirrels, guinea pigs, hamsters and porcupines.
tissue Made of cells, it is any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.
TRPV1 A type of pain receptor on cells that detects signals about painful heat.
Journal: J.H. Jeong et al. Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake. PLOS Biology. Vol. 16, published online April 24, 2018. doi: 10.1371/journal.pbio.2004399.