What nearly brainless rodents know about weight loss and hunger

To find out, 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 emerging story 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. The second this rodent looks at food, its brain starts assessing how many calories it may have. Photo / Josh Norem, The New York Times
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 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 signalling 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.
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, 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, Grill said, in an intact brain – not just a brainstem – other areas of the brain also exert control.
But, 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 Sternson, 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 quieten 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 Knight, 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,' 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 Lowell, who worked with Andermann at Beth Israel Deaconess. 'It was very unexpected.'
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.
Lowell and 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 Andermann, who repeated the experiment, when they turned the hunger neurons on, 'The mouse gets up and eats another 10 to 15% of its body weight.' He added, 'The neurons are saying, 'Just focus on food.'' Researchers could switch neurons on and off, and it would affect how much a rodent was willing to eat. Photo / Zachary Knight, Thew New York Times
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 signalled 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,' 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,' Nectow said.
This article originally appeared in The New York Times.
Written by: Gina Kolata
Photographs by: Josh Norem, Zachary Knight
©2025 THE NEW YORK TIMES

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Drug cheats: the new weight loss

More and more men are choosing to use weight-loss drugs. Joel Golby asks why. Well, I'm on Mounjaro. A few minutes ago I injected 2.5mg of it into my thigh, so it's in there, doing whatever it is that it does. It's a curious feeling to inject yourself, just in your house — despite the 17-step guide it feels illicit, wrong, dark-web, like I shouldn't be entrusted to do this to myself. It doesn't get any easier, either: this is my 11th week on the drug, and despite how carefully I follow each instruction (wipe the top of the injector with a sterile swab; screw in the one-use needle; make sure there are no air bubbles; inject), and how much I tell myself out loud "This isn't weird," it still is. I still have to take a small breath before the (slight, thin, short, delicate!) needle breaks the surface of my skin; I still feel squeamish when I take it out again; I still spend the day afterwards wondering if slithering feelings in my body are psychosomatic or not. 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1News

20-05-2025

• 1News

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He told the Washington Post the side effects were unpleasant, including bloating, intense chills and 'occasional sharp abdominal pains'. He also said these drugs could 'halt the trajectory of chronic disease in the United States if used under medical supervision and by the right people'. This book deep dives into why Kessler personally, along with millions around the world, struggles to lose weight and keep it off. He points out: "I have two advanced degrees […] I have been Dean of two medical schools. I've run the FDA. No-one would ever accuse me of not having discipline and determination." If managing weight were simply about sufficient education and willpower, Kessler – for one – would not struggle with it. But he does. His book invites readers to lay down their assumptions and be open to new ways of thinking about obesity. He is not presenting anything new. His unique contribution here is the drawing together of insights from various fields of research (addiction, endocrinology, obesity medicine), telling a compelling story about why obesity is so prevalent and difficult to treat. It is a story of many influences: including biology, psychology and even the economy. In some ways, this is a dense read. Kessler's references (at the end) take up a full third of the book. But in other ways, it's an easy read. He writes in a narrative style, weaving conversations with researchers into his personal story of struggle. In this way, he pre-empts reader arguments, showing us how his views differ from others. For example, he gives voice to the opinions of the 'Body Positivity' movement – which advocates for respect and acceptance of all body sizes – while still concluding losing weight is something we need to aim for. He recognises weight is not a cosmetic issue, but a health issue: many serious diseases, like heart failure, stroke, rheumatioid arthritis and diabetes, share obesity as a risk factor. Our society's failure to act on obesity will lead to increasing illness, Kessler argues. He backs this – and all his claims – with pages of data, which he presents in relatable forms. For example, 13 types of cancer have an increased risk with obesity. A man with a BMI greater than 40 gets nine years shaved off his life. Kessler structures the book in four parts. The first, provocatively, is about the addictive power of food. This way of viewing food underpins the rest of the book. Part 2 explains the complex biology of weight gain and loss. (Spoiler: it's not just about counting calories and exercising.) Part 3 outlines the role of GLP-1 medications in sustainable weight loss in a comprehensive, practical and nuanced way. And the final part cautions readers not to rely purely on medication, pointing to environmental factors that have led to obesity in the first place, like sedentary lifestyles and diets dominated by unhealthy foods. Humming throughout, rising to a crescendo in the last section, is the accusation of a prime mover behind the obesity epidemic: hyper-palatable foods that have been created this way on purpose by adding sugar, salt and fat. This results in both long shelf lives, and enjoyable sensations when eaten (for example: crunchy or soft). Creating these properties means significantly changing a food from its original state, or even creating it from scratch in a laboratory. He wisely refuses to get dragged into discussing 'ultra-processed foods' (UPFs), which have become a politically contentious topic. Debate around the exact definition of a 'UPF' has allowed the food industry to distract and deflect from their potential harms. By using the term 'ultra-formulated food', Kessler neatly side-steps those with a vested interest in defending UPFs. The problem, he contends, lies in the addictive qualities of ultra-formulated foods, which – coupled with diminished nutrient content – cause metabolic mayhem when we eat them. Our glucose levels spike and visceral fat builds up. Ultra-formulated foods are abundant, too. There are reasonable arguments that processing food has been essential in staving off starvation. But instead of helping us avoid illness, ultra-formulated products are 'weapons against our biology'. The FDA, his prior workplace, sets guidelines around food safety, he points out. But, he asks, why there are no regulations protecting the community from food that is heavily processed to become hyper-palatable and energy dense, but low in nutrition? Kessler's final call is directed at both individuals and communities. He calls on us to untangle ourselves from dependence on ultra-formulated foods. And he wants communities to collectively demand a healthier future. Kessler is methodical in his explanations, continually anticipating and rebutting potential arguments. Much of what he says is compelling – but the real question is what each of us chooses to do about it. His take-homes in a nutshell: ultra-formulated foods are addictive. GLP-1 injectables treat that addiction. But the ultimate solution is to regulate ultra-formulated foods in the first place. Author: Natasha Yates, General Practitioner, PhD Candidate, Bond University This article is republished from The Conversation under a Creative Commons licence.