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.
Just days after the Trump administration completed millions of dollars in renovations on the Lincoln Memorial Reflecting Pool to make it American flag-blue, residents and online users noted it had turned a phosphorescent green.
Here’s why:
The calm, still waters of the Reflecting Pool make it an ideal nursery for algae growth. Algae need nitrogen and phosphorus to grow, and the Reflecting Pool is primarily fed by the Potomac River, which gets heavy doses of those nutrients from nearby urban and agricultural lands.
The Potomac also absorbed one of the largest sewage spills in U.S. history earlier this year when a pipe burst five miles upstream of Washington, although that event probably happened too long ago to contribute to the algal bloom today.
Untreated sewage is high in nitrogen and phosphorus. When nutrient levels are high, feasting algae can quickly reproduce.
The Department of the Interior said when the algae first appeared that it was “residual,” from the supply lines to the pool.
Experts also speculate that the darker blue color may be helping the Reflecting Pool absorb more heat. The higher temperatures promote algae growth by allowing their metabolisms to shift into overdrive.
Summer temperatures in D.C. aren’t helping. This week, temperatures are as high as 95 degrees in the city, prompting a heat alert.
The combination probably explains the excessive growth, turning the water surface an opaque green and preventing onlookers from seeing the new blue hue of the concrete basin.
Algae are important and beneficial organisms when the ecosystem is in balance. They’re the base of the aquatic food chain, fed on by herbivores of all shapes and sizes, including shrimp and juvenile fish, which in turn feed organisms higher up the food chain. The single-celled organisms use the power of the sun to produce energy through photosynthesis, similar to houseplants on your balcony.
In an effort combat the algae in the Reflecting Pool, employees of the National Park Service were seen pouring in gallons of hydrogen peroxide, a chemical commonly used in pool maintenance.
The Department of the Interior also is employing a “high-tech nanobubble ozone technology” to destroy the cells of the algae.
Ozone — yes, the same irritant that is in smog — is a gas composed of three oxygen molecules, and the small size of the bubbles allow the most gas transfer into the water, where it can damage algal cells, similar to how it irritates our lungs.
This only treats the symptoms, however. Generally, ozone nanobubbling is effective as a temporary solution for algae blooms. Longer-term fixes would have to address what makes the Reflecting Pool so ideal for algae, such as its depth, darker color and inflow of nitrogen and phosphorus.
In California, ozone nanobubbles also have been used in a project to improve water quality in the Tijuana River. The 120-mile river that runs near the border in northern Mexico and Southern California was the site of a pilot study in 2025. The U.S. section of the International Boundary and Water Commission reported that the nanobubbling reduced “odors and bacteria,” but the project concluded prematurely after a flood swept some of the instrumentation into the river.
A plant extract that’s gaining popularity as a pain cure-all and has been associated with multiple California deaths in its concentrated, synthetic form has been approved for research as a treatment for opioid addiction by the federal government.
Kratom is derived from the leaves of Mitragyna speciosa, a tree native to Southeast Asia, and is commonly made into a powder or pill.
Researchers say people in the U.S. are using kratom to alleviate anxiety, treat chronic pain or as a remedy for the symptoms associated with quitting opioids, due to its ability to bind with opioid receptors in the body. But recently, public health officials have raised alarms about a component of the leaf called 7-hydroxymitragynine, also known as 7-OH, an alkaloid that has the potential for abuse and addiction in high doses.
Last year, the Los Angeles County Public Health Department linked the deaths of six county residents to the use of 7-OH mixed with other substances. The toxicology screens for some of the deceased revealed both kratom and 7-OH, leading to a countywide crackdown of products with either compound because they’re unregulated.
Although there is no scientific consensus on whether kratom has therapeutic value, the Food and Drug Administration has recommended that its potent 7-OH form be classified as a controlled substance. Consumers who use 7-OH as a pain reliever expecting an experience similar to consuming kratom are at risk, said Dr. Mason Turner, president-elect of the California Society of Addiction Medicine.
“I have a couple of patients that I work with who use 7-OH for chronic pain management, not realizing the potential of the medication, and then developed an opioid use disorder,” Turner said. “I think in that case it was very clear they were seeking it for the chronic pain, not to get high, not to have some kind of experience, but really to reduce their pain.”
About two decades ago, Turner said, the healthcare industry started acknowledging the limits and risks of prescribing opioids for chronic pain. Some doctors pulled back on prescriptions, recognizing the potential for abuse.
That led some patients to find alternative solutions, he said.
“Maybe they don’t get a good benefit, or maybe the benefit from some of the other treatments is not as robust as what they got from opioids,” Turner said. “So they seek out some of these illicit products … or they look for kratom or 7-OH to be able to mitigate the pain.”
Turner said he supports further research into kratom and regulation because “it could be worth exploring as a treatment for chronic pain.”
On June 1, the National Institutes of Health announced that researchers from the University of Florida would begin the first phase of clinical trials on kratom to evaluate it as a potential treatment for opioid addiction. The research would be done with the FDA’s approval, according to officials.
“This … is a major step toward expanding treatment options for the millions of Americans struggling with opioid use disorder, which has contributed to historically high overdose mortality rates,” said Dr. Nora Volkow, director of NIH’s National Institute on Drug Abuse, in a statement.
Interest in kratom surged in the last couple of years as users have reported consuming the compound in the form of a pill, powder or tea to treat various ailments. A John Hopkins survey conducted in 2020 reported that 91% of respondents used kratom to treat chronic pain, 67% to treat anxiety, 64% for depression and 41% to treat opioid dependence.
A more recent study by the University of Michigan and Texas State University found that more than 5 million people in the U.S., including more than 100,000 children ages 12 to 17, have used kratom, the compound experts say is growing in popularity with young adults.
In the study, which analyzed data from the National Survey on Drug Use and Health collected between 2021 and 2024, researchers say that despite numerous state-level bans on kratom across the nation, its use is at an all-time high and is increasing.
People between the ages of 21 and 34 said they used kratom at least once and 1% said they used it in the last year. The share of children ages 12 and older who said they had used kratom increased from 1.6% in 2021 to 1.9% in 2024.
The FDA has stated that neither kratom nor 7-OH are approved as drug products, dietary supplements or food additives, but that hasn’t stopped storefronts and companies from selling them as such.
Up until November you could find kratom and 7-OH products in smoke shops and specialty stores in California, but that has stopped.
“Until kratom and its pharmacologically active key ingredients mitragynine and 7-OH are approved for use, they will remain classified as adulterants in drugs, dietary supplements and foods,” the California Department of Public Health told The Times via email.
Kratom “Feel Free Classic” liquid products are displayed at a smoke shop in Los Angeles in 2024 before they were banned.
(Michael Blackshire / Los Angeles Times)
In May, the California Department of Public Health and Atty. Gen. Rob Bonta filed a complaint against Ashlynn Marketing Group Inc., accusing the company of repeatedly flouting the state’s regulations on kratom products.
The filing, submitted in the San Diego County Superior Court, seeks a judge’s order to condemn and destroy the embargoed kratom products, halt ongoing unlawful manufacturing and impose civil penalties.
The California Department of Public Health “is pursuing legal action because Ashlynn’s continued manufacture and sale of these products pose a clear and preventable public‑health risk and violates state and federal law,” said Dr. Erica Pan, the department’s director and state public health officer. “7-OH and kratom-derived products have been associated with addiction, serious health harms, overdose and death.”
The state is alleging its inspectors visited Ashlynn Marketing Group’s facility in Santee in May 2025 and found kratom powders, capsules, liquids and chewable tablets being manufactured and held for sale.
During the visit, inspectors issued an embargo to prohibit the sale and distribution of all kratom-related materials on-site, according to the complaint.
Public health inspectors conducted follow-up visits at the facility in October and April, “collecting evidence at both inspections that indicated embargoed kratom products had been moved, tampered with and repackaged,” according to public health officials.
“In addition, investigators observed evidence of continued manufacturing and distribution of kratom materials,” officials said. “The firm’s owner continues to manufacture kratom products and ships orders weekly.”
To date, the California Department of Public Health has seized more than $5 million worth of kratom and 7-OH products, a spokesperson for the department told The Times.
California and Los Angeles County are considering whether to tighten regulations or ban the compounds altogether.
NEW YORK — Scientists have unearthed communities of marine life — including jellyfish, tubeworms and brittle stars — thriving on a whale graveyard that is millions of years old.
These graveyards form when whale carcasses fall to the sea floor, becoming a sustaining snack for nearby critters. This one, located up to 23,000 feet below the surface of the southeastern Indian Ocean, spans the largest area and is so far the deepest and oldest found.
A whale’s sheer size and the unique chemistry of its bones are the keys to forming these unique underwater neighborhoods, said Xikun Song, a biologist with the Chinese Academy of Sciences’ Institute of Deep-sea Science and Engineering.
“At the same time, the very nature of the deep ocean makes these sites exceptionally difficult for scientists to locate,” Song, who was involved with the latest find, wrote in an email.
Researchers explored the remains during multiple deep-sea submersible trips in 2023, collecting samples and mapping the extent of the necropolis. They found five carcass sites and fossils, including skulls belonging to beaked and baleen whales. The oldest bones date back 5.3 million years.
Feeding and living on the carcasses were myriad creatures, large and small, including sea cucumbers, squat lobsters and saltwater clams. Many of them are likely species that have never been documented, according to findings published Wednesday in the journal Nature.
“The potential number of specimens is just astounding,” said paleontologist Stephen Godfrey with the Calvert Marine Museum in Maryland, who wasn’t involved in the research.
Many factors likely conspired to preserve the bones for millions of years, according to the study authors. They’re dense enough to outlast attacks from bone-eating worms, and located deep enough in the ocean to avoid getting buried by dust and loose particles. The bones also were coated with a light layer of minerals from the surrounding seawater, which may have prevented them from degrading.
Why did so many whales die here? Maybe they were already living in the area and died of natural causes. A few could have perished from exhaustion or illness caused by deep-sea diving. The area’s shape, akin to the letter V, could also have funneled the remains to their resting spot, the authors wrote.
Such discoveries are important because they clue scientists into the vibrant communities that find a way to live even in remote, hard-to-reach environments.
Studying the whale graveyards “is important for understanding how life can adapt to such extreme conditions, not only due to the lack of light and oxygen but also to the incredibly high pressure,” said study co-author and paleontologist Giovanni Bianucci with the University of Pisa in Italy in an email.
Ramakrishnan writes for The Associated Press.
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation.
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