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.
Science
Health insurance premiums for 1.7 million Californians on Obamacare will soar as federal subsidies end
Californians renewing their public health plans or who plan to sign up for the first time will be in for sticker shock when open enrollment begins on Saturday. Monthly premiums for federally subsidized plans available on the Covered California exchange — often referred to as Obamacare — will soar by 97% on average for 2026.
The skyrocketing premiums come as a result of a conflict at the center of the current federal government shutdown, which began on Oct. 1: a budgetary impasse between the Republican majority and Democrats over whether to preserve enhanced, Biden-era tax credits that expanded healthcare eligibility to millions more Americans and kept monthly insurance costs affordable for existing policyholders. About 1.7 million of the 1.9 million Californians currently on a Covered California plan benefit from the tax credits.
Open enrollment for the coming year runs from Nov. 1 until Jan. 31. It’s traditionally the period when members compare options and make changes to existing plans and when new members opt in.
Only this time, the government shutdown has stirred uncertainty about the fate of the subsidies, first introduced during the COVID-19 pandemic and which have been keeping policy costs low, but will expire at the end of the year if lawmakers in Washington don’t act to extend them.
Californians window shopping on the exchange’s consumer homepage will have to make some tough decisions, said Covered California Executive Director Jessica Altman. The loss of the tax credits to subsidize premiums only adds to what can already be a complicated, time-consuming and frustrating process.
Even if the subsidies remained intact, premiums for plans offered by Covered California were set to rise by roughly 10% for 2026, due to spikes in drug prices and other medical services, Altman said.
Without the subsidies, Covered California said its members who receive financial assistance will see their monthly premiums jump by an additional $125 a month, on average, for 2026.
The organization projects that the cost increases will lead many Californians to simply go without coverage.
“Californians are going to be facing a double whammy: premiums going up and tax credits going away,” Altman said. “We estimate that as many as 400,000 of our current enrollees will disenroll and effectively be priced out of the health insurance that they have today. That is a devastating outcome.”
Indeed, the premium spike threatens to lock out the very Americans that the 2010 Affordable Care Act — President Obama’s signature domestic policy win — was intended to help, said Altman. That includes people who earn too much to qualify for Medicaid but who either make too little to afford a private plan or don’t work for an employer that pays a portion of the premiums.
That’s a broad swath of Californians — including many bartenders and hairdressers, small business owners and their employees, farmers and farm workers, freelancers, ride-share drivers, and those working multiple part-time gigs to make ends meet. The policy change will also affect Californians who use the healthcare system more frequently because they have ongoing conditions that are costly to treat.
By raising the tax-credit eligibility threshold to include Americans earning more than 400% of the federal poverty level, the Biden-era subsidies at the heart of the budget stalemate have brought an estimated 160,000 additional middle-income Californians into the system, Covered California said. The enhanced subsidies save members about $2.5 billion a year overall in out-of-pocket premium expenses, according to the exchange.
California lawmakers have tried to provide some relief from rising Covered California premiums by recently allocating an additional $190 million in state-level tax credits in next year’s budget for individuals who earn up to 150% of the federal poverty level. That would keep monthly premiums consistent with 2025 levels for a person making up to $23,475 a year, or a family of four bringing in $48,225 a year, and provide partial relief for individuals and households making slightly more.
Altman said the state tax credits will help. But it may not be enough. Forecasts from the Urban Institute, a nonprofit research group and think tank, also show a significant drop-off of roughly 400,000 enrolled members in Covered California.
The national outlook is even worse. The Congressional Budget Office warned Congress nearly a year ago that if the enhanced premium subsidies were allowed to expire, the ranks of the uninsured would swell by 2.2 million nationwide in 2026 alone — and by an average of 3.8 million Americans each year from 2026 to 2034.
Organizations that provide affordable Obamacare plans are preparing for Californians to get squeezed out of the system if the expanded subsidies disappear.
L.A. Care, the county’s largest publicly operated health plan, offers Covered California policies for 230,000 mostly lower-income people. About 90% of the Covered California consumers they work with receive subsidies to offset their out-of-pocket healthcare insurance costs, said Martha Santana-Chin, L.A. Care’s CEO. “Unless something drastic happens … a lot of those people are going to fall off of their coverage,” Santana-Chin said.
That outcome would ripple far and wide, she said — thanks to two factors: human behavior and basic economics.
If more and more people choose to go uninsured, more and more people will resort to visiting hospital emergency rooms for non-emergency care, disrupting and overwhelming the healthcare system.
Healthcare providers will be forced to address the cost of treating rising numbers of uninsured people by raising the prices they bill to insurers for patients who have private plans. That means Californians who are not Covered California members and don’t receive other federal healthcare aid will eventually see their premiums spike too, as private insurers pass any added costs down to their customers.
But right now, with the subsidies set to end soon and recent changes to Medicaid eligibility requirements threatening to knock some of the lowest-income Californians off of that system, both Altman and Santana-Chin said their main concern is for those who don’t have alternatives.
In particular, they are concerned about people of color, who are disproportionately represented among low-income Californians, according to the Public Policy Institute of California. Any hike in out-of-pocket insurance costs next year could blow the budget of a family barely getting by.
“$100, $150, $200 — that’s meaningful to people living on fixed incomes,” Altman said. “Where is that money coming from when you’re living paycheck to paycheck?”
Science
Plan to kill 450,000 owls pushes past major obstacle with Republicans both for and against
A controversial plan to kill one owl species to save another cleared a major hurdle.
The full Senate on Wednesday struck down a GOP effort to prevent the cull of up to 450,000 barred owls in the Pacific Northwest over three decades, ending a saga that created strange political bedfellows.
It’s a major win for environmentalists and federal wildlife officials who want to protect northern spotted owls that have been crowded out by their larger, more aggressive cousins. In recent weeks they got an unlikely ally in loggers who said scuttling the U.S. Fish and Wildlife Service plan could hinder timber sales.
But it’s a blow to an equally unusual alliance that includes right-wing politicians and animal rights advocates who argue the cull is too expensive and inhumane. The Trump administration leaned on Republican lawmakers to get out of the way, scrambling partisan lines.
Sen. John Kennedy, a conservative from Louisiana, sought to nix the owl-killing plan via the Congressional Review Act, which can be used to overturn recent rules by federal agencies.
Kennedy said Interior Secretary Doug Burgum, whose portfolio includes timber production, recently called him and told him to abandon the resolution. This month logging advocates said that stopping the cull would jeopardize timber production goals set by the Trump administration.
But Kennedy was not persuaded.
“The secretary needed to call somebody who cared what he thought, because I think he’s wrong,” Kennedy said on the Senate floor. “I think he and the other members of the administrative state at the Department of the Interior decided to play God.”
Flanked by pictures of owls and bumbling cartoon hunter Elmer Fudd, Kennedy praised barred owls for their “soulful eyes” and “incredibly soft” feathers. But he acknowledged they’re better hunters than spotted owls. Barred owls, which moved over from eastern North America, are outcompeting spotted owls for food and shelter in their native territory.
Louisiana Senator John Kennedy spearheaded a resolution to overturn the Biden-era plan to cull barred owls, even after he said the Trump administration told him to back down.
(Senate Banking Committee)
Ultimately the resolution failed 72 to 25, with three lawmakers not voting. Nearly all those who voted in favor of the resolution were Republican, but even more Republicans voted against it. The Fish and Wildlife Service approved the barred owl cull last year under the Biden Administration.
“I feel a lot of relief because this was one of the most major threats to the long-term, continued existence of the northern spotted owl in many years,” said Tom Wheeler, executive director of the Environmental Protection Information Center. “We’ve passed this hurdle, which isn’t to say there aren’t other hurdles or road bumps up ahead, but this feels good.”
Wheeler described the failed effort as a “nuclear threat” — if the resolution had passed, the Fish and Wildlife Service would have been blocked from pursuing any similar rule, unless explicitly authorized by Congress.
Now Wheeler said he and his allies will continue to push for the owl cull to be carried out, and for federal funding to support it.
Animal welfare advocates like Wayne Pacelle, president of Animal Wellness Action and Center for a Humane Economy, are dismayed.
“What this means is that not only are barred owls at extreme risk of large-scale shooting, but spotted owls and old-growth forests are at risk from chainsaws,” Pacelle said of the failed resolution.
Pacelle’s camp vowed to continue the fight. A lawsuit challenging the hunt they filed against the federal government last fall is moving forward. And they’ll try to ensure money doesn’t flow to the program.
In May, federal officials canceled three related grants in California totaling more than $1.1 million, including one study that would have included lethally removing barred owls from more than 192,000 acres in Mendocino and Sonoma counties.
However, there are other projects to kill barred owls in the Golden State, according to Peter Tira, a spokesperson for the California Department of Fish and Wildlife.
One $4.3-million grant issued by the state agency will support barred owl removal in the northwestern part of the state, along with other research. Another grant issued by NASA to a university involves killing barred owls in California as well as creating a tool to prioritize areas where the raptors need to be managed.
It’s not clear how or if the government shutdown, now stretching into its 31st day, is affecting the projects, Tira said in an email.
Science
Families pay thousands for an unproven autism treatment. Researchers say we need ethical guidelines for marketing the tech
Over the last decade, clinics have popped up across Southern California and beyond advertising something called magnetic e-resonance therapy, or MERT, as a therapy for autism.
Developed by the Newport Beach-based company Wave Neuroscience, MERT is based on transcranial magnetic stimulation, a type of brain stimulation that’s approved by the Food and Drug Administration to treat depression, obsessive-compulsive disorder, migraines and smoking addiction.
Clinics licensing MERT have claimed that their trademarked version of the treatment can also produce “miraculous results” in kids with autism, improving their sleep, emotional regulation and communication abilities. A six-week course of MERT sessions typically costs $10,000 or more.
The FDA hasn’t approved MERT for this use. However, prescribing drugs or devices for conditions they aren’t approved for, which is known as off-label prescribing, is a legal and common practice in medicine.
But when such treatments are offered to vulnerable people, a group of researchers argue in a new peer-reviewed editorial in the medical journal Transcranial Magnetic Stimulation, they should be evidence-based, clearly explained to patients and priced in a way that reflects the likelihood that they will work as advertised.
Most clinics advertising off-label TMS as a therapy for autism don’t meet those standards, the researchers say.
Autism is “the biggest off-label business … [and] the one that is the greatest concern,” said Dr. Andrew Leuchter, director of UCLA’s TMS Clinical and Research Service.
Leuchter is one of three researchers with TMS expertise who recently called for the establishment of ethical guidelines around off-label TMS marketing in the field’s primary journal.
Written with Lindsay Oberman, director of the Neurostimulation Research Program at the National Institute of Mental Health, and Dr. Holly Lisanby, founder of the NIMH Noninvasive Neuromodulation Unit and dean of Arizona State University’s School of Medicine and Advanced Medical Engineering, the editorial singles out MERT as an “example of off-label TMS where there is negligible evidence of efficacy.”
“There is extremely limited scientific evidence at present that any form of TMS has efficacy and safety in improving the core symptoms of language, social skills, or behavioral disturbances associated with [Autism Spectrum Disorder],” the editorial states. “Websites and other promotional materials that fail to acknowledge this limited evidence-base can create a risk of bias and potential for false expectations.”
Dr. Erik Won, Wave’s president and chief medical officer, did not respond to requests for comment.
A Times investigation last year found there are no large scientific studies demonstrating that MERT is significantly better than a placebo at improving speech and communication challenges associated with autism. Wave has not conducted any clinical trials on MERT and autism.
Won said last year that Wave is working to obtain funding “for further studies and ultimately an FDA indication.”
Websites for clinics offering MERT often feature written testimonials from parents describing what they saw as positive changes in their children’s moods or spoken-language abilities after treatment sessions.
Without data, however, there is no way to know whether a patient’s anecdotal experience is typical or an outlier, according to Zoe Gross of the Autistic Self Advocacy Network, a nonprofit group run by and for autistic adults.
“Be wary of therapies that are sold to you with testimonials. If you go to a clinic website and they have dozens of quotes from parents saying, ‘This changed my child’s life in XYZ ways,’ that isn’t the same as evidence,” Gross told The Times last year.
A therapy could have only a 1% success rate, she said, and still yield dozens of positive testimonials once thousands of people have tried it.
For families unsure of whether a particular commercial therapy might be valuable for their child, “ask the advice of a clinician or an autism scientist who is not connected to the facility providing a service, just to get a frank appraisal of whether it’s likely to be helpful or likely to be worth the money,” said James McPartland, director of the Yale Center for Brain and Mind Health, who is currently studying the relationship between TMS and social perception in autistic adults. “Before you want to ask someone to spend resources on it, you want to have a certain degree of confidence [that] it’s going to be useful.”
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