Science
What Nearly Brainless Rodents Know About Weight Loss and Hunger
Do we really have free will when it comes to eating? It’s a vexing question that is at the heart of why so many people find it so difficult to stick to a diet.
To get answers, one neuroscientist, Harvey J. Grill of the University of Pennsylvania, turned to rats and asked what would happen if he removed all of their brains except their brainstems. The brainstem controls basic functions like heart rate and breathing. But the animals could not smell, could not see, could not remember.
Would they know when they had consumed enough calories?
To find out, Dr. Grill dripped liquid food into their mouths.
“When they reached a stopping point, they allowed the food to drain out of their mouths,” he said.
Those studies, initiated decades ago, were a starting point for a body of research that has continually surprised scientists and driven home that how full animals feel has nothing to do with consciousness. The work has gained more relevance as scientists puzzle out how exactly the new drugs that cause weight loss, commonly called GLP-1s and including Ozempic, affect the brain’s eating-control systems.
The story that is emerging does not explain why some people get obese and others do not. Instead, it offers clues about what makes us start eating, and when we stop.
While most of the studies were in rodents, it defies belief to think that humans are somehow different, said Dr. Jeffrey Friedman, an obesity researcher at Rockefeller University in New York. Humans, he said, are subject to billions of years of evolution leading to elaborate neural pathways that control when to eat and when to stop eating.
As they have probed how eating is controlled, researchers learned that the brain is steadily getting signals that hint at how calorically dense a food is. There’s a certain amount of calories that the body needs, and these signals make sure the body gets them.
The process begins before a lab animal takes a single bite. Just the sight of food spurs neurons to anticipate whether a lot of calories will be packed into that food. The neurons respond more strongly to a food like peanut butter — loaded with calories — than to a low-calorie one like mouse chow.
The next control point occurs when the animal tastes the food: Neurons calculate the caloric density again from signals sent from the mouth to the brainstem.
Finally, when the food makes its way to the gut, a new set of signals to the brain lets the neurons again ascertain the caloric content.
And it is actually the calorie content that the gut assesses, as Zachary Knight, a neuroscientist at the University of California San Francisco, learned.
He saw this when he directly infused three types of food into the stomachs of mice. One infusion was of fatty food, another of carbohydrates and the third of protein. Each infusion had the same number of calories.
In each case, the message to the brain was the same: The neurons were signaling the amount of energy, in the form of calories, and not the source of the calories.
When the brain determines enough calories were consumed, neurons send a signal to stop eating.
Dr. Knight said these discoveries surprised him. He’d always thought that the signal to stop eating would be “a communication between the gut and the brain,” he said. There would be a sensation of having a full stomach and a deliberate decision to stop eating.
Using that reasoning, some dieters try to drink a big glass of water before a meal, or fill up on low-calorie foods, like celery.
But those tricks have not worked for most people because they don’t account for how the brain controls eating. In fact, Dr. Knight found that mice do not even send satiety signals to the brain when all they are getting is water.
It is true that people can decide to eat even when they are sated, or can decide not to eat when they are trying to lose weight. And, Dr. Grill said, in an intact brain — not just a brainstem — other areas of the brain also exert control.
But, Dr. Friedman said, in the end the brain’s controls typically override a person’s conscious decisions about whether they feel a need to eat. He said, by analogy, you can hold your breath — but only for so long. And you can suppress a cough — but only up to a point.
Scott Sternson, a neuroscientist with the University of California in San Diego and Howard Hughes Medical Institute, agreed.
“There is a very large proportion of appetite control that is automatic,” said Dr. Sternson, who is also a co-founder of a startup company, Penguin Bio, that is developing obesity treatments. People can decide to eat or not at a given moment. But, he added, maintaining that sort of control uses a lot of mental resources.
“Eventually, attention goes to other things and the automatic process will wind up dominating,” he said.
As they probed the brain’s eating-control systems, researchers were continually surprised.
They learned, for example, about the brain’s rapid response to just the sight of food.
Neuroscientists had found in mice a few thousand neurons in the hypothalamus, deep in the brain, that responded to hunger. But how are they regulated? They knew from previous studies that fasting turned these hunger neurons on and that the neurons were less active when an animal was well fed.
Their theory was that the neurons were responding to the body’s fat stores. When fat stores were low — as happens when an animal fasts, for example — levels of leptin, a hormone released from fat, also are low. That would turn the hunger neurons on. As an animal eats, its fat stores are replenished, leptin levels go up, and the neurons, it was assumed, would quiet down.
The whole system was thought to respond only slowly to the state of energy storage in the body.
But then three groups of researchers, independently led by Dr. Knight, Dr. Sternson and Mark Andermann of Beth Israel Deaconess Medical Center, examined the moment-to-moment activity of the hunger neurons.
They began with hungry mice. Their hunger neurons were firing rapidly, a sign the animals needed food.
The surprise happened when the investigators showed the animals food.
“Even before the first bite of food, the activity of those neurons shut off,” Dr. Knight said. “The neurons were making a prediction. The mouse looks at food. The mouse predicts how many calories it will eat.”
The more calorie-rich the food, the more neurons turn off.
“All three labs were shocked,” said Dr. Bradford B. Lowell, who worked with Dr. Andermann at Beth Israel Deaconess. “It was very unexpected.”
Dr. Lowell then asked what might happen if he deliberately turned off the hunger neurons even though the mice hadn’t had much to eat. Researchers can do this with genetic manipulations that mark neurons so they can turn them on and off with either a drug or with a blue light.
These mice would not eat for hours, even with food right in front of them.
Dr. Lowell and Dr. Sternson independently did the opposite experiment, turning the neurons on in mice that had just had a huge meal, the mouse equivalent of a Thanksgiving dinner. The animals were reclining, feeling stuffed.
But, said Dr. Andermann, who repeated the experiment, when they turned the hunger neurons on, “The mouse gets up and eats another 10 to 15 percent of its body weight.” He added, “The neurons are saying, ‘Just focus on food.’”
Researchers continue to be amazed by what they are finding — layers of controls in the brain that ensure eating is rigorously regulated. And hints of new ways to develop drugs to control eating.
One line of evidence was discovered by Amber Alhadeff, a neuroscientist at the Monell Chemical Senses Center and the University of Pennsylvania. She recently found two separate groups of neurons in the brainstem that respond to the GLP-1 obesity drugs.
One group of neurons signaled that the animals have had enough to eat. The other group caused the rodent equivalent of nausea. The current obesity drugs hit both groups of neurons, she reports, which may be a factor in the side effects many feel. She proposes that it might be possible to develop drugs that hit the satiety neurons but not the nausea ones.
Alexander Nectow, of Columbia University, has another surprise discovery. He identified a group of neurons in the brainstem that regulate how big a meal is desired, tracking each bite of food. “We don’t know how they do it,” he said.
“I’ve been studying this brainstem region for a decade and a half,” Dr. Nectow said, “but when we went and used all of our fancy tools, we found this population of neurons we had never studied.”
He’s now asking if the neurons could be targets for a class of weight loss drugs that could upstage the GLP-1s.
“That would be really amazing,” Dr. Nectow said.
When danger calls, some animals bare their teeth. Others take to the sky, or curl into protective balls. But the remora — a fish that often hitches a ride on larger marine animals like sea turtles, whales and sharks — sometimes follows a less dignified strategy: It disappears inside a manta ray’s rear end.
In a study published on Monday in the journal Ecology and Evolution, a team of researchers referred to this newly observed behavior as “cloacal diving.” While many questions about this fishy practice remain, there is one thing the team feels sure about.
“It does not look like the manta ray likes it,” said Catherine Macdonald, director of the shark research and conservation program at the University of Miami and senior author of the new study.
While remoras, also known as suckerfish, have been observed diving into the safety of whale-shark cloacae in the past, this is the first time anyone has documented the behavior in manta rays.
The paper uses seven instances of cloacal diving that took place between 2010 and 2025 across all three known species of manta ray. What’s more, the observations, which were gathered by the Marine Megafauna Foundation, occurred in three separate ocean basins, suggesting that this previously unobserved behavior could be common among rays and the remora species that associate with them.
In some cases, the remora forces itself so far inside the ray’s cloaca that only the very tip of its tail can be seen protruding from the exterior. In others, the ray is not large enough to accommodate the remora’s entire body, and half of the suckerfish hangs out of the ray, like a toddler playing peekaboo beneath a blanket.
“The remoras are pretty much as wide as the cloaca is,” said Emily Yeager, a Ph.D. student at the University of Miami and the lead author of the study. “So it’s fully filling that opening.”
To the researchers’ knowledge, no one has studied how sensitive manta ray cloacae are specifically, though Dr. Macdonald said that her lab would often swab the cloacae of sharks for fecal DNA to better understand what they’d been eating.
“They don’t especially like us sticking a swab up there,” she said. “And that swab is a big Q-Tip compared to a remora.”
While all of this may seem as if it’s a lark — News flash: Fish hides inside another fish’s backside — the findings contribute new information to a topic already hotly debated by scientists: the type of impact remoras have on their hosts.
Traditionally, experts have seen the interaction between remoras and manta rays as either commensal or mutualistic. In a commensal relationship, one animal benefits while the other is neither benefited nor harmed. In a mutualistic relationship, both creatures benefit: The remora gets a free ride and food, while the manta has its skin cleaned of parasites.
But cloacal diving almost certainly changes the equation, said Eleanor Caves, a sensory biologist at Brown University who was not affiliated with the new study. While the remora’s presence inside the ray is most likely brief, it could interfere with waste discharge or reproduction, or even damage the cloaca’s lining. This may mean the relationship between remoras and manta rays sometimes tilts into a parasitic interaction, in which one species benefits and the other is harmed.
While the researchers provide just seven instances of remoras using manta-ray cloacae as their own personal panic rooms, the fact that the animals are so difficult to see once inside suggests that the behavior is under-documented, at the very least.
“It’s really challenging to study these highly mobile relationships in marine systems,” Ms. Yeager said. “Oftentimes when researchers interact with these organisms, it’s just for a second in time, when we’re scuba diving in one location and one passes over us, or we’re fishing in a site and we bring one to our boat.”
“But these relationships persist 24/7, all of the time,” she added. “And we’re seeing just a snapshot.”
A Bay Area resident who was stuck on a cruise ship during a deadly hantavirus outbreak has returned to Santa Clara County and is being monitored by health officials.
The Santa Clara County Public Health Department confirmed Sunday that a county resident has returned to California after being exposed to the Andes hantavirus while on the MV Hondius. Three people on board the luxury cruise ship have died, and at least nine others have suspected cases.
The California resident is being monitored in coordination with the California Department of Public Health and the Centers for Disease Control and Prevention, the agency said.
CDPH acknowledged in a statement Friday that one California resident had already returned home, but didn’t disclose where they lived. The agency said another Californian remained on the ship as of Friday.
“At this time, there is no known risk to the public in Santa Clara County,” said Sarah Rudman, director of the Santa Clara County Public Health Department.
The CDC has emphasized that the risk to the American public “is extremely low” as American passengers stuck on the ship begin to return home.
Hantavirus is a rare disease typically transmitted to humans through inhalation of particles contaminated with the urine, droppings or saliva from a rodent.
Passengers began disembarking the ship Sunday in the Canary Islands. The CDC says it has sent a team to conduct a risk assessment for each American passenger.
Mandy Rosenberg, 35, from Brookfield, Wisc., has always drawn attention because of her looks. With her long blonde hair, athletic build and large blue eyes, she was called Barbie by some of her high school peers.
But even though people often told her that she was pretty, she didn’t view herself the same way.
She’d spend hours staring at a tiny blemish on her forehead that was barely visible to others. In her mind, it was a large and unsightly scar, and she would climb on top of her bathroom sink to get as close to the mirror as possible while examining it.
“If I couldn’t make that go away, I didn’t want to live anymore,” she said.
Ms. Rosenberg didn’t know it at the time, but she had both obsessive-compulsive disorder and body dysmorphic disorder, or B.D.D., a mental health condition that causes people to spend an inordinate amount of time worrying about their appearance — to the point where they may isolate themselves from others and feel imprisoned in their own bodies.
People with B.D.D. not only think they look unattractive but can become convinced that others will reject them because of their flaws.
“They often feel they’re unlovable,” said Dr. Katharine Phillips, an expert in B.D.D. and a psychiatrist at Weill Cornell Medicine and NewYork-Presbyterian.
What is body dysmorphic disorder?
Those with B.D.D. fixate on perceived cosmetic problems that to others appear unnoticeable or minor. But it’s not about vanity; instead, people with B.D.D. feel extreme anguish that impairs their functioning.
The disorder typically emerges during adolescence and is estimated to affect 2 to 3 percent of the general population, but these numbers may be conservative because the disorder is underdiagnosed.
Studies have shown differences in the brains of people with B.D.D., said Dr. Jamie Feusner, a professor of psychiatry at the University of Toronto Temerty Faculty of Medicine. Some of his research has found that in those who have the condition areas of the brain that help us view things holistically are underactive.
This might be part of the reason that people with B.D.D. have trouble viewing their imperfections as small relative to their entire face or body. It’s akin to looking at a window with a smudge on it, then “thinking that the whole window is ruined,” Dr. Feusner said.
Patients with B.D.D. aren’t always aware that their concerns stem from a mental health problem. Instead, they often believe wholeheartedly that they have physical defects.
Because of this, someone might suffer for a decade or more before seeking help from a mental health provider, said Hilary Weingarden, a psychologist in Massachusetts who studies O.C.D. and related conditions.
Instead, “they’re going to their dermatologist and a plastic surgeon and the dentist and the aesthetician,” she said.
But trying to “fix” their appearance only serves to maintain and exacerbate their anxiety in the long run.
What are the signs and symptoms?
People with B.D.D. may withdraw from relationships, avoid attending work or school, and spend an excessive amount of time on repetitive behaviors like examining themselves in the mirror, attempting to camouflage their appearance or seeking reassurance from others.
Chris Trondsen, a therapist in Costa Mesa, Calif., who diagnosed Ms. Rosenberg with B.D.D., said his patients admit to spending hours chatting with artificially intelligent bots, both seeking affirmation and asking what they ought to fix.
“If you ask a human, people are going to get fed up answering the questions,” Mr. Trondsen said.
Mr. Trondsen was inspired to study psychotherapy because of his own struggle with B.D.D. He used to fixate on his complexion and other parts of his body, too. He worried that his nose was too large for his face and that his body wasn’t muscular enough, a form of B.D.D. called muscle dysmorphia.
“I kept thinking I was getting uglier,” Mr. Trondsen said.
Like many patients with B.D.D., he also spent hours checking his body in mirrors and rarely left his apartment. At 21 years old, Mr. Trondsen became so isolated and consumed by his appearance that he attempted suicide, and might have died had his roommate not discovered him. After that, he sought help and was diagnosed with O.C.D. and B.D.D.
It’s common for those with B.D.D. to also have conditions like O.C.D., major depressive disorder, social phobia and substance use disorder. Studies indicate that people with B.D.D. have high rates of suicidal ideation and behavior, too. One meta-analysis found that, across a patient’s life span, about 66 percent of those with B.D.D. will have thoughts of suicide and around 35 percent will attempt it.
How is it treated?
Cognitive behavioral therapy for B.D.D. has been shown to lead to remission in more than half of patients. It includes exposure and response prevention, which is meant to help patients gradually confront the things that they have been avoiding or the rituals they have become dependent upon, like hiding parts of their body with clothing or makeup.
Therapists try to help patients view themselves more holistically, emphasizing that there’s more to them than the specific parts of their bodies they scrutinize.
The disorder can also be treated with serotonin reuptake inhibitors, or S.R.I.s., often at high doses. For those with severe B.D.D., both medication and C.B.T. are recommended, Dr. Phillips said.
For Ms. Rosenberg, cognitive behavioral therapy with her former therapist, Mr. Trondsen, gradually helped her condition.
Later, as part of her treatment, she created a diagram showcasing all of the things that contribute to her identity: She is a daughter and a faithful Christian, she loves dogs and cats, she is a teacher, she is caring — she is more than just her looks.
My body, she said, “doesn’t get to determine how I go about my day.”
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