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
California’s summer COVID wave shows signs of waning. What are the numbers in your community?
There are some encouraging signs that California’s summer COVID wave might be leveling off.
That’s not to say the seasonal spike is in the rearview mirror just yet, however. Coronavirus levels in California’s wastewater remain “very high,” according to the U.S. Centers for Disease Control and Prevention, as they are in much of the country.
But while some COVID indicators are rising in the Golden State, others are starting to fall — a hint that the summer wave may soon start to decline.
Statewide, the rate at which coronavirus lab tests are coming back positive was 11.72% for the week that ended Sept. 6, the highest so far this season, and up from 10.8% the prior week. Still, viral levels in wastewater are significantly lower than during last summer’s peak.
The latest COVID hospital admission rate was 3.9 hospitalizations for every 100,000 residents. That’s a slight decline from 4.14 the prior week. Overall, COVID hospitalizations remain low statewide, particularly compared with earlier surges.
The number of newly admitted COVID hospital patients has declined slightly in Los Angeles County and Santa Clara County, but ticked up slightly up in Orange County. In San Francisco, some doctors believe the summer COVID wave is cresting.
“There are a few more people in the hospitals, but I think it’s less than last summer,” said Dr. Peter Chin-Hong, a UC San Francisco infectious diseases expert. “I feel like we are at a plateau.”
Those who are being hospitalized tend to be older people who didn’t get immunized against COVID within the last year, Chin-Hong said, and some have a secondary infection known as superimposed bacterial pneumonia.
Los Angeles County
In L.A. County, there are hints that COVID activity is either peaking or starting to decline. Viral levels in local wastewater are still rising, but the test positivity rate is declining.
For the week that ended Sept. 6, 12.2% of wastewater samples tested for COVID in the county were positive, down from 15.9% the prior week.
“Many indicators of COVID-19 activity in L.A. County declined in this week’s data,” the L.A. County Department of Public Health told The Times on Friday. “While it’s too early to know if we have passed the summer peak of COVID-19 activity this season, this suggests community transmission is slowing.”
Orange County
In Orange County, “we appear to be in the middle of a wave right now,” said Dr. Christopher Zimmerman, deputy medical director of the county’s Communicable Disease Control Division.
The test positivity rate has plateaued in recent weeks — it was 15.3% for the week that ended Sept. 6, up from 12.9% the prior week, but down from 17.9% the week before that.
COVID is still prompting people to seek urgent medical care, however. Countywide, 2.9% of emergency room visits were for COVID-like illness for the week that ended Sept. 6, the highest level this year, and up from 2.6% for the week that ended Aug. 30.
San Diego County
For the week that ended Sept. 6, 14.1% of coronavirus lab tests in San Diego County were positive for infection. That’s down from 15.5% the prior week, and 16.1% for the week that ended Aug. 23.
Ventura County
COVID is also still sending people to the emergency room in Ventura County. Countywide, 1.73% of ER patients for the week that ended Sept. 12 were there to seek treatment for COVID, up from 1.46% the prior week.
San Francisco
In San Francisco, the test positivity rate was 7.5% for the week that ended Sept. 7, down from 8.4% for the week that ended Aug. 31.
“COVID-19 activity in San Francisco remains elevated, but not as high as the previous summer’s peaks,” the local Department of Public Health said.
Silicon Valley
In Santa Clara County, the coronavirus remains at a “high” level in the sewershed of San José and Palo Alto.
Roughly 1.3% of ER visits for the week that ended Sunday were attributed to COVID in Santa Clara County, down from the prior week’s figure of 2%.
Science
Early adopters of ‘zone zero’ fared better in L.A. County fires, insurance-backed investigation finds
As the Eaton and Palisades fires rapidly jumped between tightly packed houses, the proactive steps some residents took to retrofit their homes with fire-resistant building materials and to clear flammable brush became a significant indicator of a home’s fate.
Early adopters who cleared vegetation and flammable materials within the first five feet of their houses’ walls — in line with draft rules for the state’s hotly debated “zone zero” regulations — fared better than those who didn’t, an on-the-ground investigation from the Insurance Institute for Business and Home Safety published Wednesday found.
Over a week in January, while the fires were still burning, the insurance team inspected more than 250 damaged, destroyed and unscathed homes in Altadena and Pacific Palisades.
On properties where the majority of zone zero land was covered in vegetation and flammable materials, the fires destroyed 27% of homes; On properties with less than a quarter of zone zero covered, only 9% were destroyed.
The Insurance Institute for Business and Home Safety, an independent research nonprofit funded by the insurance industry, performed similar investigations for Colorado’s 2012 Waldo Canyon fire, Hawaii’s 2023 Lahaina fire and California’s Tubbs, Camp and Woolsey fires of 2017 and 2018.
While a handful of recent studies have found homes with sparse vegetation in zone zero were more likely to survive fires, skeptics say it does not yet amount to a scientific consensus.
Travis Longcore, senior associate director and an adjunct professor at the UCLA Institute of the Environment and Sustainability, cautioned that the insurance nonprofit’s results are only exploratory: The team did not analyze whether other factors, such as the age of the homes, were influencing their zone zero analysis, and how the nonprofit characterizes zone zero for its report, he noted, does not exactly mirror California’s draft regulations.
Meanwhile, Michael Gollner, an associate professor of mechanical engineering at UC Berkeley who studies how wildfires destroy and damage homes, noted that the nonprofit’s sample does not perfectly represent the entire burn areas, since the group focused specifically on damaged properties and were constrained by the active firefight.
Nonetheless, the nonprofit’s findings help tie together growing evidence of zone zero’s effectiveness from tests in the lab — aimed at identifying the pathways fire can use to enter a home — with the real-world analyses of which measures protected homes in wildfires, Gollner said.
A recent study from Gollner looking at more than 47,000 structures in five major California fires (which did not include the Eaton and Palisades fires) found that of the properties that removed vegetation from zone zero, 37% survived, compared with 20% that did not.
Once a fire spills from the wildlands into an urban area, homes become the primary fuel. When a home catches fire, it increases the chance nearby homes burn, too. That is especially true when homes are tightly packed.
When looking at California Department of Forestry and Fire Protection data for the entirety of the two fires, the insurance team found that “hardened” homes in Altadena and the Palisades that had noncombustable roofs, fire-resistant siding, double-pane windows and closed eaves survived undamaged at least 66% of the time, if they were at least 20 feet away from other structures.
But when the distance was less than 10 feet, only 45% of the hardened homes escaped with no damage.
“The spacing between structures, it’s the most definitive way to differentiate what survives and what doesn’t,” said Roy Wright, president and chief executive of the Insurance Institute for Business and Home Safety. At the same time, said Wright, “it’s not feasible to change that.”
Looking at steps that residents are more likely to be able to take, the insurance nonprofit found that the best approach is for homeowners to apply however many home hardening and defensible space measures that they can. Each one can shave a few percentage points off the risk of a home burning, and combined, the effect can be significant.
As for zone zero, the insurance team found a number of examples of how vegetation and flammable materials near a home could aid the destruction of a property.
At one home, embers appeared to have ignited some hedges a few feet away from the structure. That heat was enough to shatter a single pane window, creating the perfect opportunity for embers to enter and burn the house from the inside out. It miraculously survived.
At others, embers from the blazes landed on trash and recycling bins close to the houses, sometimes burning holes through the plastic lids and igniting the material inside. In one instance, the fire in the bin spread to a nearby garage door, but the house was spared.
Wooden decks and fences were also common accomplices that helped embers ignite a structure.
California’s current zone zero draft regulations take some of those risks into account. They prohibit wooden fences within the first five feet of a home; the state’s zone zero committee is also considering whether to prohibit virtually all vegetation in the zone or to just limit it (regardless, well-maintained trees are allowed).
On the other hand, the draft regulations do not prohibit keeping trash bins in the zone, which the committee determined would be difficult to enforce. They also do not mandate homeowners replace wooden decks.
The controversy around the draft regulations center around the proposal to remove virtually all healthy vegetation, including shrubs and grasses, from the zone.
Critics argue that, given the financial burden zone zero would place on homeowners, the state should instead focus on measures with lower costs and a significant proven benefit.
“A focus on vegetation is misguided,” said David Lefkowith, president of the Mandeville Canyon Assn.
At its most recent zone zero meeting, the Board of Forestry and Fire Protection directed staff to further research the draft regulations’ affordability.
“As the Board and subcommittee consider which set of options best balance safety, urgency, and public feasibility, we are also shifting our focus to implementation and looking to state leaders to identify resources for delivering on this first-in-the-nation regulation,” Tony Andersen, executive officer of the board, said in a statement. “The need is urgent, but we also want to invest the time necessary to get this right.”
Home hardening and defensible space are just two of many strategies used to protect lives and property. The insurance team suspects that many of the close calls they studied in the field — homes that almost burned but didn’t — ultimately survived thanks to firefighters who stepped in. Wildfire experts also recommend programs to prevent ignitions in the first place and to manage wildlands to prevent intense spread of a fire that does ignite.
For Wright, the report is a reminder of the importance of community. The fate of any individual home is tied to that of those nearby — it takes a whole neighborhood hardening their homes and maintaining their lawns to reach herd immunity protection against fire’s contagious spread.
“When there is collective action, it changes the outcomes,” Wright said. “Wildfire is insidious. It doesn’t stop at the fence line.”
Science
Notorious ‘winter vomiting bug’ rising in California. A new norovirus strain could make it worse
The dreaded norovirus — the “vomiting bug” that often causes stomach flu symptoms — is climbing again in California, and doctors warn that a new subvariant could make even more people sick this season.
In L.A. County, concentrations of norovirus are already on the rise in wastewater, indicating increased circulation of the disease, the local Department of Public Health told the Los Angeles Times.
Norovirus levels are increasing across California, and the rise is especially notable in the San Francisco Bay Area and L.A., according to the California Department of Public Health.
And the rate at which norovirus tests are confirming infection is rising nationally and in the Western U.S. For the week that ended Nov. 22, the test positivity rate nationally was 11.69%, up from 8.66% two months earlier. In the West, it was even worse: 14.08%, up from 9.59%, according to the U.S. Centers for Disease Control and Prevention.
Norovirus is extraordinarily contagious, and is America’s leading cause of vomiting and diarrhea, according to the CDC. Outbreaks typically happen in the cooler months between November and April.
Clouding the picture is the recent emergence of a new norovirus strain — GII.17. Such a development can result in 50% more norovirus illness than typical, the CDC says.
“If your immune system isn’t used to something that comes around, a lot of people get infected,” said Dr. Peter Chin-Hong, an infectious diseases expert at UC San Francisco.
During the 2024-25 winter season, GII.17 overthrew the previous dominant norovirus strain, GII.4, that had been responsible for more than half of national norovirus outbreaks over the preceding decade. The ancestor of the GII.17 strain probably came from a subvariant that triggered an outbreak in Romania in 2021, according to CDC scientists.
GII.17 vaulted in prominence during last winter’s norovirus surge and was ultimately responsible for about 75% of outbreaks of the disease nationally.
The strain’s emergence coincided with a particularly bad year for norovirus, one that started unusually early in October 2024, peaked earlier than normal the following January and stretched into the summer, according to CDC scientists writing in the journal Emerging Infectious Diseases.
During the three prior seasons, when GII.4 was dominant, norovirus activity had been relatively stable, Chin-Hong said.
Norovirus can cause substantial disruptions — as many parents know all too well. An elementary school in Massachusetts was forced to cancel all classes on Thursday and Friday because of the “high volume of stomach illness cases,” which was suspected to be driven by norovirus.
More than 130 students at Roberts Elementary School in Medford, Mass., were absent Wednesday, and administrators said there probably wouldn’t be a “reasonable number of students and staff” to resume classes Friday. A company was hired to perform a deep clean of the school’s classrooms, doorknobs and kitchen equipment.
Some places in California, however, aren’t seeing major norovirus activity so far this season. Statewide, while norovirus levels in wastewater are increasing, they still remain low, the California Department of Public Health said.
There have been 32 lab-confirmed norovirus outbreaks reported to the California Department of Public Health so far this year. Last year, there were 69.
Officials caution the numbers don’t necessarily reflect how bad norovirus is in a particular year, as many outbreaks are not lab-confirmed, and an outbreak can affect either a small or large number of people.
Between Aug. 1 and Nov. 13, there were 153 norovirus outbreaks publicly reported nationally, according to the CDC. During the same period last year, there were 235.
UCLA hasn’t reported an increase in the number of norovirus tests ordered, nor has it seen a significant increase in test positivity rates. Chin-Hong said he likewise hasn’t seen a big increase at UC San Francisco.
“Things are relatively still stable clinically in California, but I think it’s just some amount of time before it comes here,” Chin-Hong said.
In a typical year, norovirus causes 2.27 million outpatient clinic visits, mostly young children; 465,000 emergency department visits, 109,000 hospitalizations, and 900 deaths, mostly among seniors age 65 and older.
People with severe ongoing vomiting, profound diarrhea and dehydration may need to seek medical attention to get hydration intravenously.
“Children who are dehydrated may cry with few or no tears and be unusually sleepy or fussy,” the CDC says. Sports drinks can help with mild dehydration, but what may be more helpful are oral rehydration fluids that can be bought over the counter.
Children under the age of 5 and adults 85 and older are most likely to need to visit an emergency room or clinic because of norovirus, and should not hesitate to seek care, experts say.
“Everyone’s at risk, but the people who you worry about, the ones that we see in the hospital, are the very young and very old,” Chin-Hong said.
Those at highest risk are babies, because it doesn’t take much to cause potentially serious problems. Newborns are at risk for necrotizing enterocolitis, a life-threatening inflammation of the intestine that virtually only affects new babies, according to the National Library of Medicine.
Whereas healthy people generally clear the virus in one to three days, immune-compromised individuals can continue to have diarrhea for a long time “because their body’s immune system can’t neutralize the virus as effectively,” Chin-Hong said.
The main way people get norovirus is by accidentally drinking water or eating food contaminated with fecal matter, or touching a contaminated surface and then placing their fingers in their mouths.
People usually develop symptoms 12 to 48 hours after they’re exposed to the virus.
Hand sanitizer does not work well against norovirus — meaning that proper handwashing is vital, experts say.
People should lather their hands with soap and scrub for at least 20 seconds, including the back of their hands, between their fingers and under their nails, before rinsing and drying, the CDC says.
One helpful way to keep track of time is to hum the “Happy Birthday” song from beginning to end twice, the CDC says. Chin-Hong says his favorite is the chorus of Kelly Clarkson’s “Since U Been Gone.”
If you’re living with someone with norovirus, “you really have to clean surfaces and stuff if they’re touching it,” Chin-Hong said. Contamination is shockingly easy. Even just breathing out little saliva droplets on food that is later consumed by someone else can spread infection.
Throw out food that might be contaminated with norovirus, the CDC says. Noroviruses are relatively resistant to heat and can survive temperatures as high as 145 degrees.
Norovirus is so contagious that even just 10 viral particles are enough to cause infection. By contrast, it takes ingesting thousands of salmonella particles to get sick from that bacterium.
People are most contagious when they are sick with norovirus — but they can still be infectious even after they feel better, the CDC says.
The CDC advises staying home for 48 hours after infection. Some studies have even shown that “you can still spread norovirus for two weeks or more after you feel better,” according to the CDC.
The CDC also recommends washing laundry in hot water.
Besides schools, other places where norovirus can spread quickly are cruise ships, day-care centers and prisons, Chin-Hong said.
The most recent norovirus outbreak on a cruise ship reported by the CDC is on the ship AIDAdiva, which set sail on Nov. 10 from Germany. Out of 2,007 passengers on board, 4.8% have reported being ill. The outbreak was first reported on Nov. 30 following stops that month at the Isle of Portland, England; Halifax, Canada; Boston; New York City; Charleston, S.C.; and Miami.
According to CruiseMapper, the ship was set to make stops in Puerto Vallarta on Saturday, San Diego on Tuesday, Los Angeles on Wednesday, Santa Barbara on Thursday and San Francisco between Dec. 19-21.
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