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
As mosquitoes go year-round in L.A., a promising fix hits a snag
Residents were supposed to get a respite from the ankle-nipping mosquitoes that fueled a recent surge in dengue fever in Los Angeles County.
Typically, the invasive mosquitoes — called Aedes aegypti — essentially disappear from winter until early May in the region.
Instead, complaints to local agencies tasked with controlling the pests spiked recently.
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“We have not seen them go away altogether like they have in previous years,” said Susanne Kluh, general manager for the Greater Los Angeles County Vector Control District.
Their unusual presence adds to the urgency of work going on in a 40-foot shipping container tucked away in Pacoima. It’s about to transform into a bustling nursery for tens of thousands of mosquitoes.
This May, the district is set for the third year in a row to release legions of sterilized male mosquitoes — which don’t bite — into parts of Sunland-Tujunga.
The last two years were promising, with the female population in two treated neighborhoods plunging by an average of more than 80%.
Yet business owners have signaled they’re not willing to pay to expand it.
That’s thrown uncertainty into officials’ goal of eventually bringing the approach to their whole service area, spanning 36 cities and unincorporated communities.
Steve Vetrone, assistant general manager at the Greater L.A. district.
(Ronaldo Bolanos / Los Angeles Times)
“Unfortunately, that’s going to be a rather expensive endeavor,” said Steve Vetrone, an assistant general manager for the district. “I can tell you right now that’s not something that we can do with our current operating budget.”
A need, an ask and a disappointing answer
Aedes aegypti are a new-ish local fixture. Native to Africa, the black-and-white striped mosquitoes were first detected in California in 2013 and landed in L.A. County the following year.
“Despite our best efforts, they’ve been able to just outpace us, and they’re now in every city and community within our district,” and all of Southern California, Vetrone said. In fact, the low-flying, day-biting mosquitoes are present in nearly half of California’s counties, including Shasta in the far north.
Desperate to find a solution, many are trying the so-called sterile insect technique — including vector control districts serving Orange and San Bernardino counties, as well as the San Gabriel Valley — and “we kind of all hope that this is going to be our silver bullet,” Kluh said.
The idea is fairly simple: unleash sterile males so that they far outnumber wild ones — say, 10 to 1 or even 100 to 1. The goal is for the altered males to mate with females, producing eggs that don’t hatch.
Kluh’s district uses X-rays to sterilize males but there are other methods, such as using genetically modified insects or ones infected with bacteria.
Female mosquitoes are fed different types of blood — pig and cow — to see which leads to the most eggs.
(Ronaldo Bolanos / Los Angeles Times)
The technique, while promising, requires time and money.
In California, property owners foot the bill for local mosquito (and other pest) control, with some paying an annual fee called a benefit assessment.
Levying a new fee requires approval from home, apartment and business owners, in accordance with Proposition 218.
To unleash sterile male mosquitoes in a broader swath of the Greater L.A. district, officials are seeking up to $20 a year per single family home. That would be on top of $18.97 that homeowners now pay for the agency’s services.
Last April, the district sent out 50,000 sample ballots to property owners, asking if they’d support the increase.
Only 47% of those returned were in favor.
“Data showed that single family homeowners were pretty supportive, but fewer business owners with larger parcels and potentially higher dues did not see the benefit in the additional expense,” Kluh said in an email.
Business owners might not live in the area, but their vote — if their property spans several acres — is weighted more heavily.
Times readers, commenting on a story from last year about the proposal, responded favorably.
“I hate mosquitos because they love me so much,” one reader said. “I would happily spend $20 to reduce their populations! I probably spend more [than] that on repellent.”
Officials haven’t given up, and plan to send out another round of sample ballots next year.
Kluh already has talking points for businesses in her back pocket: Restaurant owners should have an interest in making outdoor dining more pleasant, while apartment owners could lose revenue if their renters are sickened by an outbreak of Zika, chikungunya or yellow fever — all diseases transmitted by Aedes aegypti, she said.
Making mosquitoes that can’t reproduce
On a recent tour of the Pacoima insectary, Nicolas Tremblay, a senior vector ecologist with the district, whipped out a small container filled with a handful of what looked like vitamins.
But the clear pill cases were filled with about 6,500 mosquito eggs and bovine liver powder.
Nicolas Tremblay, senior vector ecologist, tapes trays to indicate pill capsules filled with mosquito eggs were placed in water.
(Ronaldo Bolanos / Los Angeles Times)
The pills are dropped into trays of water, where the eggs hatch and the larvae feed on the powder. It takes about nine days to go from egg to buzzing adult.
The males are then chauffeured to Garden Grove, where they’re zapped with X-rays. Then they’re driven back and set free the next day.
“It’s crazier around August, September, is when we’ll probably reach our peak production” of up to 72,000 mosquitoes a week, he said. “All these [trays] would be full of water and mosquitoes.”
In 2024, the district launched its pilot, releasing nearly 600,000 sterilized males in two Sunland-Tujunga neighborhoods over about five months.
The population of Aedes aegypti females dropped by an average of 82% compared with a control area.
The stakes became clear that year, when California reported 18 locally acquired dengue cases — a sharp rise from the first-ever cases confirmed the year before.
Last year, the pilot saw similar success, though there was also a natural drop in activity districtwide.
On the recent visit to the insectary, several hundred mosquitoes flew around in white mesh cages, serving as participants in a study to see which blood they prefer — pig or cow.
“We haven’t completed the trials yet, but it seems like they didn’t care,” he said.
One thing scientists already know: Aedes aegypti love biting people.
A highly adaptive foe
The invasive mosquitoes can lay their eggs in tiny amounts of water. A bottle cap or crease in a potato chip bag is fair game.
What’s more, mosquitoes in the Greater L.A. district are resistant to a lot of pesticides.
Now, there might be a new concern. Typically, the invasive mosquitoes go into a type of hibernation every year.
Kluh said it appeared that they may have mutated in a way that allows them to stay active through the winter.
A warming climate has already expanded their season and allowed them to move into formerly inhospitable regions.
Releasing sterilized males involves no pesticides, and also leverages the insect’s biology: Males in lust are adept at finding females.
Many residents are thrilled by the promising tool, but others bristle at the idea of manipulating nature.
“There’s folks that are in favor and then there are folks that are just absolutely opposed because it’s like, ‘You’re playing God,’” Vetrone said.
Science
Record Heat Meets a Major Snow Drought Across the West
At this point in a typical year, as the seasons officially turn from winter to spring, snowpack would still be accumulating across the Mountain West.
But this winter wasn’t typical, even before a heat wave this past week. It was the warmest on record for six Western states. Snow cover is the lowest level on record for the Colorado River Basin, and across much of the rest of the West, there are record or near-record low amounts of snow.
That alone would create a challenging year for water managers, who rely on slow and steady snowmelt to feed streams, rivers and reservoirs and meet spring and summer demand for irrigation and drinking water. While rainfall runs off quickly and can more readily evaporate from soil, snowpack serves as a valuable and lasting source of moisture and accounts for a majority of water supplies across the region, as much as 80 percent in some areas.
Current snowpack compared to historical averages
The intense heat wave threatens to make water management all the more challenging.
Much of the thin snowpack was already “ready to melt” before the heat set in, said Jon Meyer, assistant state climatologist at the Utah Climate Center. “This is the nail in the coffin.”
It’s unusual to see the whole West like this, said Leanne Lestak, an associate senior scientist at the University of Colorado Boulder who specializes in mapping snow and how much water it holds.
In early March, Ms. Lestak and her team found that vast majority of the Western United States had less than two-thirds of the amount of snow typical for this time of year, with few exceptions. In Arizona and parts of Nevada, New Mexico and Oregon, snowpack was less than a quarter of what it would usually be.
“The situation is pretty dire,” Dr. Meyer said.
The heat wave is also increasing the already-elevated fire risk across some drought-stricken areas. In Nebraska, drought set the stage for the largest wildfire in state history, which broke out last week and has not yet been contained.
The conditions that led to this year’s low snowpack are unusual, too. Snow droughts often develop from dry weather patterns that starve the West of any significant precipitation during the winter, said Dan McEvoy, a climatologist at the Desert Research Institute and Western Regional Climate Center.
But in many places, it wasn’t necessarily a dry year, he said. Instead, temperatures have been so warm that precipitation has fallen as rain, rather than snow, even at higher elevations.
Many of the mountaintops could still see some more snowfall. But as Cody Moser, a hydrologist with the Colorado Basin River Forecast Center in Salt Lake City, looks ahead to predicting how the spring will go, he doesn’t foresee any significant change in weather patterns. Now he’s expecting peak snowmelt flows to occur earlier than ever recorded in many locations, he said this week.
“I think it’s highly likely we’ve seen peak snowpack,” Mr. Moser said.
Snowpack feeding the Colorado River reaches historic lows
Even after a winter that was the warmest on record for Arizona, New Mexico, Colorado, Utah, Wyoming and Oregon, the heat that set in across much of the West this past week was extreme. Meteorologists said they were expecting to set record highs for the month of March in many locations, and the earliest arrivals of 100-degree temperatures in records that go back more than a century.
Across the Colorado River Basin, even at elevations as high as 10,000 feet, temperatures were forecast to surge into the 50s and 60s Fahrenheit on Friday and Saturday, Mr. Moser said, some 15 to 20 degrees warmer than average.
Relatively light winds and dry air over the region could limit snowmelt to some degree, he said, but the warmth and sunshine may prevent some moisture from ever reaching stream beds, said John Fleck, a water policy expert at the University of New Mexico.
“A lot of it is going to evaporate off before it even has a chance to hit the stream,” Mr. Fleck said.
This heat wave is so extreme that it would only be expected to occur once about every 500 years in the current climate, according to World Weather Attribution, a group of scientists who study links between extreme weather events and climate change.
“These temperatures are completely off the scale for March, and our data shows that they would be virtually impossible in a world without human-caused climate change,” said Ben Clarke, a research associate in extreme weather and climate change at Imperial College London.
In places like the Colorado Front Range, home to the majority of that state’s population, snowpack serves as the largest source of water. For the utility Denver Water, snowpack usually contains significantly more water than its largest surface reservoir, said Taylor Winchell, the agency’s climate adaptation program lead.
Denver Water has enough supply to handle a low-water year, but the snowpack conditions are creating “very high levels of concern,” Mr. Winchell said. The Denver Water Board is poised to officially declare Stage One drought restrictions, asking residents to significantly reduce their outdoor watering. If the snow drought were to repeat for multiple years, the problem could compound and worsen, he said.
The snow drought occurs at a critical time for the larger Colorado River Basin. An agreement among the basin’s seven states over how to divide its water expired at the end of last year, and negotiations to develop a new water plan fell apart last month. (The states are also obligated to share a small portion of the water with Mexico.)
The snow drought is complicating that work. Snowpack from the river’s Upper Basin, across mountains of Colorado, Utah, New Mexico and Wyoming, accounts for a majority of the river’s natural flow each year. Declining spring precipitation and rising temperatures have caused the Colorado’s flow to decrease by nearly 20 percent over the past quarter century.
Recent forecasts estimated that inflows to Lake Powell, a key reservoir that straddles the Utah-Arizona border, will be the third-smallest on record. The lake’s surface could drop to a critical level for hydroelectric power production by the end of this year, affecting a power grid that serves seven states.
Officials at the Bureau of Reclamation, the federal agency that oversees the Colorado River and its reservoirs, declined to be interviewed but said in a statement they were monitoring hydrologic conditions to guide decisions about how to manage the Colorado River system.
Mr. Fleck said a crisis without precedent could be brewing. While a drought that hit the basin in 2002 was worse, it was relatively more manageable than what the West now faces: “We’re having one of the worst years in many decades, but with no cushion of reservoir storage to fall back on to bail us out.”
Science
New report on L.A. post-fire beach contamination finds something unexpected: good news
Researchers investigating the long-term effects of the 2025 firestorms on L.A.’s beaches have found that rarest of things: good news.
In the year following the Palisades and Eaton fires, levels of harmful metals like lead in coastal sand and seawater have remained far below California’s limits for safe drinking water and the U.S. Environmental Protection Agency’s safety thresholds for aquatic life.
“We’re not seeing any evidence for harm in the ecosystem or harm for human health,” said Noelle Held, a University of Southern California marine biogeochemist and principal investigator for the CLEAN Waters project, which is measuring post-fire water quality.
The Palisades and Eaton fires burned more than 40,000 acres and destroyed at least 12,000 buildings, blanketing the ocean in ash for up to 100 miles offshore. Heavy rains a few weeks later washed the charred remnants of plastics, batteries, cars, chemicals and other potentially toxic material into the sea and up onto beaches via the region’s massive network of storm drains and concrete-lined rivers.
Initial testing by the nonprofit environmental group Heal the Bay in the weeks after the fires documented a spike in lead, mercury and other heavy metals in coastal waters. Concentrations of beryllium, copper, chromium, nickel and lead in particular were significantly above established safety thresholds for marine life, prompting fears for the long-term health of fish, marine mammals and the marine food chain.
For their most recent study, Held’s team analyzed seawater samples collected along multiple locations on five different dates between Feb. 10 and Oct. 17 in 2025, along with sand collected in August.
Seawater lead concentrations were highest in the month after the fire and in October, when the season’s first major rain had just washed months’ worth of urban pollution into the ocean.
Even at their peak, lead levels barely surpassed 1 microgram per liter — well below the U.S. Environmental Protection Agency’s aquatic life safety threshold of 8.1 micrograms per liter.
While levels of iron, manganese and cobalt were higher in sampling locations near the Palisades burn scar than they were in other areas, even there they remain well below concentrations that could pose harm to human or marine life.
For beach sand collected in August, lead levels never topped 14 parts per million at any location, significantly below both the current California residential soil standard of 80 parts per million and the stricter 55 parts per million standard proposed by environmental health researchers.
“This isn’t something we would flag if we were testing your soil in your yard,” Held said.
The recent findings are consistent with water quality tests the State Water Resources Control Board conducted earlier in 2025. A board spokesperson said those found both higher relative concentrations of metals closest to the burn scars and no overall evidence that post-fire pollution poses an ongoing threat to human health.
Yet the need for continued testing remains. Officials struggled to answer questions about post-fire beach safety in part because of a lack of historical data on pollution levels, a pitfall researchers would like to forestall before another disaster arrives.
Future rainstorms could also continue to wash metals into Will Rogers Beach and the Rustic Creek outfall, both of which are near the Palisades burn scar, CLEAN Waters warned.
“Post-fire impacts can change over time, depending on rainfalls, runoffs and sediment movements,” said Eugenia Ermacora, manager of the nonprofit Surfrider Foundation’s L.A. chapter, which has partnered with Held’s team to collect samples. “It’s not just about the fires, but it’s about urbanization and how much our city needs to continue the work of doing testing in the water.”
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