Intakes of dietary fibre as well as high-quality and total carbohydrates in midlife were favourably linked to healthy aging and other positive health outcomes in older women, according to a new study appearing in the journal JAMA Network Open.
“We’ve all heard that different carbohydrates can affect health differently, whether for weight, energy, or blood sugar levels. But rather than just look at the immediate effects of these macronutrients, we wanted to understand what they might mean for good health 30 years later,” said Andres Ardisson Korat, a scientist at Tufts University and lead author of the study. “Our findings suggest that carbohydrate quality may be an important factor in healthy aging.”
Researchers from Tufts University and Harvard T.H. Chan School of Public Health analysed data from Nurses’ Health Study questionnaires collected every four years between 1984 and 2016. They examined the midlife diets and eventual health outcomes of more than 47 000 women who were between the ages of 70 and 93 in 2016. Intakes of total carbohydrates, refined carbohydrates, high-quality (unrefined) carbohydrates, carbohydrates from whole grains, fruits, vegetables, and legumes, dietary fibre, and the dietary glycaemic index and glycaemic load were derived from the validated food-frequency questionnaires. The researchers defined healthy aging as the absence of 11 major chronic diseases, lack of cognitive and physical function impairments, and having good mental health, as self-reported in the Nurses’ Health Study questionnaires. In the new study, 3706 participants met the healthy aging definition.
The analysis showed intakes of total carbohydrates, high-quality carbohydrates from whole grains, fruits, vegetables, and legumes, and total dietary fibre in midlife were linked to 6 to 37% greater likelihood of healthy aging and several areas of positive mental and physical health. In the other direction, intakes of refined carbohydrates (carbohydrates from added sugars, refined grains, and potatoes) and starchy vegetables were associated with 13% lower odds of healthy aging.
“Our results are consistent with other evidence linking consumption of fruits and vegetables, whole grains, and legumes with lower risks of chronic diseases, and now we see the association with physical and cognitive function outcomes,” said senior author Qi Sun, associate professor in the departments of nutrition and epidemiology at Harvard Chan School.
The authors note as a limitation that the study population was composed mostly of white health professionals; future research will be necessary to replicate these findings in more diverse cohorts.
Ardisson Korat also noted that additional work is needed to understand the potential mechanisms linking dietary fiber and high-quality carbohydrates to healthy aging.
“Studies are starting to find an association between food choices in midlife and quality of life in later years. The more we can understand about healthy aging, the more science can help people live healthier for longer,” added Ardisson Korat.
Throwing a little heat on your meal might be an effective strategy for cutting back on calories, according to a new study led by researchers at Penn State.
Scientists at the University’s Sensory Evaluation Center examined how increasing “oral burn” – the spicy taste from ingredients like chili pepper – affects how much food people consume during a meal. The findings, available online now and slated to publish in the October issue of the journalFood Quality and Preference, suggest that making the meal slightly spicier led participants to eat less, consuming fewer calories.
“We know from previous studies that when people slow down, they eat significantly less,” said Paige Cunningham, a postdoctoral researcher and lead author on the study who earned her doctorate in nutritional sciences from Penn State in 2023. “We suspected that making a meal spicier might slow people down. We thought, let’s test, under controlled experimental conditions in the lab, if adding a small amount of spice, but not so much that the meal is inedible, will make people eat slower and therefore eat less.”
The researchers found that increasing spiciness slightly using dried chili pepper slowed down eating and reduced the amount of food and energy consumed at a meal, all without negatively affecting the palatability of the dish.
“This points to added chilies as a potential strategy for reducing the risk of energy overconsumption,” said John Hayes, Penn State professor of food science and corresponding author on the paper. “While portion control wasn’t the explicit goal of this study, our results suggest this might work. Next time you’re looking to eat a little less, try adding a blast of chilies, as it may slow you down and help you eat less.”
A vitamin supplement that improves metabolism in the eye appears to slow down damage to the optic nerve in glaucoma. Promising results have been published in the journal Cell Reports Medicine. The researchers behind the study have now started a clinical trial on patients.
In glaucoma, the optic nerve is gradually damaged, leading to vision loss and, in the worst cases, blindness. High pressure in the eye drives the disease, and eye drops, laser treatment or surgery are therefore used – with varying effect – to lower the pressure in the eye and thus slow down the disease.
Glaucoma researchers have long theorised that the substance homocysteine is somehow relevant to understanding the disease. Now, researchers at Karolinska Institutet have investigated the role of homocysteine in several ways. In the current study, the researchers discovered that when rats with glaucoma were given elevated levels of homocysteine, their disease did not worsen.
Investigated metabolic pathways
The researchers also found that high levels of homocysteine in the blood of people with glaucoma did not correlate with how quickly the disease progressed, and that glaucoma was not more common in people with a genetic susceptibility to forming high levels of homocysteine. Based on these findings, the researchers concluded that homocysteine does not drive the disease but is a consequence of it.
Since homocysteine is a natural part of the body’s metabolism, the researchers wanted to investigate metabolic pathways involving homocysteine in both rodents and humans with glaucoma. They then saw several abnormalities, the most important of which were metabolic changes linked to the retina’s ability to use certain vitamins. This change meant that metabolism was slowed down locally in the retina – and this played a role in the development of the disease.
“Our conclusion is that homocysteine is a bystander in the disease process, not a player. Altered homocysteine levels may reveal that the retina has lost its ability to use certain vitamins that are necessary to maintain healthy metabolism. That’s why we wanted to investigate whether supplements of these vitamins could protect the retina”, says co-lead on the paper James Tribble, researcher and assistant professor at the Department of Clinical Neuroscience at Karolinska Institutet.
Promising results lead to clinical trial
In experiments on mice and rats with glaucoma, the researchers gave supplements of the B vitamins B6, B9 and B12, as well as choline. This had a positive effect. In mice that had a slower developing glaucoma, the damage to the optic nerve was completely halted. In rats, which had a more aggressive form of the disease with faster progression, the disease was slowed down.
In these experiments, eye pressure was left untreated, which the researchers highlight as particularly interesting – it suggests that the vitamin mix affects the disease in a different way than lowering eye pressure does.
“The results are so promising that we have started a clinical trial, with patients already being recruited at S:t Eriks Eye Hospital in Stockholm”, says James Tribble.
Both patients with primary open-angle glaucoma (slower progression) and pseudoexfoliation glaucoma (faster progression) are included.
Intermittent fasting is not only a useful tool for weight loss, it’s also shown to have many benefits for metabolic health – independent of weight loss. Yet many people may find intermittent fasting to be a challenge, especially if following the 5:2 version of the diet where calories are severely restricted two days a week.
But my latest study shows that you don’t need to severely restrict your calories to get the metabolic benefits of intermittent fasting. Even just restricting the number of carbs you eat twice a week may be enough to improve your metabolic health.
Intermittent fasting appears to be so beneficial for health because of the way it alters our metabolism.
After a meal, our body enters the postprandial state. While in this state, our metabolism pushes our cells to use carbohydrates for immediate energy, while storing some of these carbs as well as fat for later use. But after several hours without food, in the postabsorptive “fasted” state, our metabolism switches to using some of our fat stores for energy.
In this regard, intermittent fasting ensures a better balance between the sources it uses for energy. This leads to improved metabolic flexibility, which is linked with better cardiometabolic health. In other words, this means lower risk of cardiovascular disease, insulin resistance and type 2 diabetes.
My colleagues and I previously ran a study to demonstrate the effects of a fast on the body. We observed that following a day of both total fasting or severe calorie restriction (eating around only 25% of each person’s daily calorie requirements), the body was better at clearing and burning the fat of a full English breakfast the next day. Fasting shifted the body from using carbs to using fat. This effect carried on both during the fast and the next day.
Our research has also compared the effects of intermittent fasting to a calorie-matched or calorie-restricted diet. Both groups followed the diet until they lost 5% of their body weight.
Despite both groups losing the same 5% of body weight, and at the same rate, the intermittent fasting group had greater improvements in their metabolic handling, similar to what we saw in the previous trial.
Other researchers who have compared the effects of the 5:2 variant of the intermittent fasting diet to a calorie-matched, calorie-restricted diet have also found fasting is beneficial for metabolic health.
For people who follow the 5:2 intermittent fasting diet, typical fasting days are, by their nature, very low in calories – equating to only a few hundred calories per day. Because people are consuming so few calories on fasting days, it also means they’re consuming very few carbohydrates. Given the postprandial state is governed by carbohydrate availability, this begged the question as to whether it’s the calorie restriction or the carbohydrate restriction that’s creating the metabolic effect when intermittent fasting.
We recruited 12 overweight and obese participants. Participants were first given a very low-carb diet one day. Another day, they were given a severely calorie-restricted diet (around 75% fewer calories than they’d normally eat). After each fasting day, we gave them a high-fat, high-sugar meal (similar to an English breakfast) to see how easily their bodies burned fat.
What we found was that the shift to fat burning and improved fat handling of the high-calorie meal were near identical following both the traditional calorie-restricted “fast” day and the low-carb day. In other words, restricting carbs can elicit the same favourable metabolic effects as fasting.
It will be important now for more studies to be conducted using a larger cohort of participants to confirm these findings.
Such findings may help us address some of the practical problems we face with intermittent fasting and traditional low-carb diets.
The other limitation of both intermittent fasting and continuous carb restriction is that weight loss is a likely outcome. Hence these approaches are not universally beneficial for those who need to improve their health without losing weight or those looking to maintain their weight.
We are now testing the feasibility of an intermittent carb restriction diet, or a low-carb 5:2. So instead of restricting calories two days a week, you would restrict the number of carbs you consume twice a week. If this is proven to be beneficial, it would offer the benefits of fasting without restricting calories on “fast” days.
Cinnamon is one of the oldest and most commonly used spices in the world – but a new study from the University of Mississippi indicates a compound in it could interfere with some prescription medications.
In a recent study published in Food Chemistry: Molecular Sciences, the researchers found that cinnamaldehyde, a primary component of cinnamon, activates receptors that control the metabolic clearance of medication from the body, meaning consuming large amounts of cinnamon could reduce the effects of drugs.
“Health concerns could arise if excessive amounts of supplements are consumed without the knowledge of health care provider or prescriber of the medications,” said Shabana Khan, a principal scientist in the natural products centre. “Overconsumption of supplements could lead to a rapid clearance of the prescription medicine from the body, and that could result in making the medicine less effective.”
Aside from its culinary uses, cinnamon has a long history of being used in traditional medicine and can help manage blood sugar and heart health and reduce inflammation. But how the product actually functions in the body remains unclear.
Sprinkling cinnamon on your morning coffee is unlikely to cause an issue, but using highly concentrated cinnamon as a dietary supplement might.
“Despite its vast uses, very few reports were available to describe the fate of its major component – cinnamaldehyde,” Khan said. “Understanding its bioaccessibility, metabolism and interaction with xenobiotic receptors was important to evaluate how excess intake of cinnamon would affect the prescription drugs if taken at the same time.”
Not all cinnamon is equal. Cinnamon oil – which is commonly used topically as an antifungal or antibacterial and as a flavouring agent in food and drinks – presents almost no risk of herb-drug interactions, said Amar Chittiboyina, the center’s associate director.
But cinnamon bark – especially Cassia cinnamon, a cheaper variety of cinnamon that originates in southern China – contains high levels of coumarin, a blood thinner, compared to other cinnamon varieties. Ground Cassia cinnamon bark is what is normally found in grocery stores.
“In contrast, true cinnamon from Sri Lanka carries a lower risk due to its reduced coumarin content,” he said. “Coumarin’s anticoagulant properties can be hazardous for individuals on blood thinners.”
More research is needed to fully understand the role that cinnamon plays in the body and what potential herb-drug interactions may occur, said Bill Gurley, a principal scientist in the Ole Miss center and co-author of the study.
“We know there’s a potential for cinnamaldehyde to activate these receptors that can pose a risk for drug interactions,” he said. “That’s what could happen, but we won’t know exactly what will happen until we do a clinical study.”
Until those studies are complete, the researchers recommend anyone interested in using cinnamon as a dietary supplement to check with their doctor first.
“People who suffer from chronic diseases – like hypertension, diabetes, cancer, arthritis, asthma, obesity, HIV, AIDS or depression – should be cautious when using cinnamon or any other supplements,” Khan said. “Our best advice is to talk to a health care provider before using any supplements along with the prescription medicine.
“By definition, supplements are not meant to treat, cure or mitigate any disease.”
Even vegans who get enough total protein may fall short for some essential amino acids
In New Zealand study, 3 in 4 vegans ate sufficient protein, but half didn’t meet daily lysine and leucine requirements
In a new study of people with long-term vegan diets, most ate an adequate amount of total daily protein, but a significant proportion did not meet required levels of the amino acids lysine and leucine. Bi Xue Patricia Soh and colleagues at Massey University, New Zealand, present these findings in the open-access journal PLOS One on April 16, 2025.
Proteins are made up of various molecular “building blocks” known as amino acids. While the human body can synthesise most of the amino acids we need to live, we completely rely on the food we eat to provide the nine “indispensable amino acids” we cannot make ourselves. Typically, plant-based foods have more varied levels of indispensable amino acids that the body can use, as compared to animal-sourced foods, so they are of particular concern in vegan diets.
However, most prior research on protein in vegan diets has not considered specific amino acids nor the digestibility of different foods, which accounts for the fact that not all of what we eat, including amino acids, is fully utilised by the body.
To help deepen understanding of amino acid intake in vegan diets, Soh and colleagues analysed detailed, four-day food diaries kept by 193 long-term vegans living in New Zealand. They used information from the United States Department of Agriculture and the New Zealand FoodFiles database to calculate participants’ intake of different amino acids from the different foods they ate.
The analysis showed that about three quarters of participants met daily total protein requirements. Accounting for body weight, intake of all indispensable amino acids also met requirements.
However, when considering digestibility, only about half of the participants met daily requirements for lysine and leucine levels, making them the most limiting indispensable amino acids in the study. Among the food types consumed by participants, legumes and pulses were the biggest contributors to overall protein and lysine intake.
These findings underscore that meeting total daily protein requirements does not necessarily mean meeting indispensable amino acid requirements. On the basis of their findings, the researchers call for future research to explore how intake of leucine and lysine could be boosted for vegans in a nutritionally balanced manner.
The authors add: “Vegan diets are the most restrictive form of plant-based eating, relying entirely on plant sources for all nutrients. Achieving high protein quality on a vegan diet requires more than just consuming enough protein – it also depends on the right balance and variety of plant foods to supply all the amino acids in the quantities that our body needs. Prolonged deficiencies in these essential nutrients can negatively affect overall protein balance, muscle maintenance and other physiological functions, especially in more vulnerable populations.”
“In our study, lysine and leucine were the most commonly under-consumed amino acids in our vegan cohort and fall below the daily requirements needed by our body. This is because many plant foods generally contain lower quantities of these amino acids that can be absorbed and utilised by the body. However, the inclusion of legumes, nuts and seeds emerged as valuable plant sources – not only to support overall protein intake but also to specifically increase lysine and leucine quantities in a vegan diet.”
A new study from Mass General Brigham suggests that eating only during the daytime could help people avoid the health risks associated with shift work. Results are published in Nature Communications.
“Our prior research has shown that circadian misalignment – the mistiming of our behavioral cycle relative to our internal body clock – increases cardiovascular risk factors,” said senior author Frank A.J.L. Scheer, PhD, a professor of Medicine at Brigham and Women’s Hospital. “We wanted to understand what can be done to lower this risk, and our new research suggests food timing could be that target.”
Animal studies have shown that aligning food timing with the internal body clock could mitigate the health risks of staying awake during the typical rest time, which prompted Scheer and his colleagues to test this concept in humans.
For the study, researchers enlisted 20 healthy young participants to a two-week in-patient study at the Brigham and Women’s Center for Clinical Investigation. They had no access to windows, watches, or electronics that would clue their body clocks into the time. The effect of circadian misalignment could be determined by comparing how their body functions changed from before to after simulated night work.
Study participants followed a “constant routine protocol,” a controlled laboratory setup that can tease apart the effects of circadian rhythms from those of the environment and behaviours (eg, sleep/wake, light/dark patterns). During this protocol, participants stayed awake for 32 hours in a dimly lit environment, maintaining constant body posture and eating identical snacks every hour. After that, they participated in simulated night work and were assigned to either eating during the nighttime (as most night workers do) or only during the daytime. Finally, participants followed another constant routine protocol to test the aftereffects of the simulated night work. Importantly, both groups had an identical schedule of naps, and, thus, any differences between the groups were not due to differences in sleep schedule.
The investigators examined the aftereffects of the food timing on participants’ cardiovascular risk factors and how these changed after the simulated night work. Researchers measured various cardiovascular risk factors, including autonomic nervous system markers, plasminogen activator inhibitor-1 (which increases the risk of blood clots), and blood pressure.
Remarkably, these cardiovascular risk factors increased after simulated night work compared to the baseline in the participants who were scheduled to eat during the day and night. However, the risk factors stayed the same in the study participants who only ate during the daytime, even though how much and what they ate was not different between the groups—only when they ate.
Limitations of the study include that the sample size was small, although of a typical size for such highly controlled and intensive randomised controlled trials. Moreover, because the study lasted two weeks, it may not reflect the chronic risks of nighttime versus daytime eating.
A strength is that the study participants’ sleep, eating, light exposure, body posture, and activity schedule were so tightly controlled.
“Our study controlled for every factor that you could imagine that could affect the results, so we can say that it’s the food timing effect that is driving these changes in the cardiovascular risk factors,” said Sarah Chellappa, MD, MPH, PhD, an associate professor at the University of Southampton, and lead author for the paper.
While further research is necessary to show the long-term health effects of daytime versus nighttime eating, Scheer and Chellappa said the results are “promising” and suggest that people could improve their health by adjusting food timing. They add that avoiding or limiting eating during nighttime hours may benefit night workers, those who experience insomnia or sleep-wake disorders, individuals with variable sleep/wake cycles, and people who travel frequently across time zones.
Researchers from the University of Missouri have discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries and endives, may support nerve cell health and holds promise as a potential treatment for ALS. Photo: Pixabay CC0
A natural compound found in everyday fruits and vegetables may hold the key to protecting nerve cells — and it’s showing promise as a potential treatment for ALS and dementia, according to new research from the University of Missouri.
“It’s exciting to discover a naturally occurring compound that may help people suffering from ALS or dementia,” Smita Saxena, a professor of physical medicine and rehabilitation at the School of Medicine and lead author of the study, said. “We found this compound had a strong impact in terms of maintaining motor and muscle function and reducing muscle atrophy.”
The study, which appears in Acta Neurologica, discovered that kaempferol, a natural antioxidant found in certain fruits and vegetables, such as kale, berries and endives, may support nerve cell health and holds promise as a potential treatment for ALS.
In lab-grown nerve cells from ALS patients, the compound helped the cells produce more energy and eased stress in the protein-processing center of the cell called the endoplasmic reticulum. Additionally, the compound improved overall cell function and slowed nerve cell damage. Researchers found that kaempferol worked by targeting a crucial pathway that helps control energy production and protein management — two functions that are disrupted in individuals with ALS.
“I believe this is one of the first compounds capable of targeting both the endoplasmic reticulum and mitochondria simultaneously,” Saxena said. “By interacting with both of these components within nerve cells, it has the potential to elicit a powerful neuroprotective effect.”
The challenge
The catch? The body doesn’t absorb kaempferol easily, and it could take a large amount to see real benefits in humans. For instance, an individual with ALS would need to consume at least 4.5kg of kale in a day to obtain a beneficial dose.
“Our bodies don’t absorb kaempferol very well from the vegetables we eat,” Saxena said. “Because of this, only a small amount reaches our tissues, limiting how effective it can be. We need to find ways to increase the dose of kaempferol or modify it so it’s absorbed into the bloodstream more easily.”
Another hurdle is getting the compound into the brain. The blood-brain barrier — a tightly locked layer of cells that blocks harmful substances — also makes it harder for larger molecules like kaempferol to pass through.
What’s next?
Despite its challenges, kaempferol remains a promising candidate for treating ALS, especially since it works even after symptoms start. It also shows potential for other neurodegenerative diseases including Alzheimer’s and Parkinson’s.
To make the compound easier for the body to absorb, Saxena’s team at the Roy Blunt NextGen Precision Health building is exploring ways to boost its uptake by neurons. One promising approach involves packaging lipid-based nanoparticles — tiny spherical particles made of fats that are commonly used in drug delivery.
“The idea is to encapsulate kaempferol within lipid-based nanoparticles that are easily absorbed by the neurons,” Saxena said. “This would target kaempferol to neurons to greatly increase its beneficial effect.”
The team is currently generating the nanoparticles with hopes of testing them by the end of the year.
Emerging evidence suggests that lycopene—a natural plant extract—may have antidepressant properties. New research in Food Science & Nutrition reveals the mechanisms behind its antidepressant effects.
Lycopene is a carotenoid, related to beta-carotene and gives some vegetables and fruits (eg, tomatoes, grapefruit) a red colour. Lycopene is a powerful antioxidant that might help protect cells from damage.
In mice with depressive-like behaviours, brain analyses revealed impairments in the hippocampus. Lycopene treatment lessened these impairments and reversed the animals’ depressive-like traits.
Lycopene treatment boosted the expression of brain-derived neurotrophic factor (BDNF), a protein with roles in many aspects of brain function. Experiments indicated that a signalling pathway involving BDNF (called the BDNF-TrkB pathway, which helps regulate learning, memory, and communication between neurons) is inhibited in mice with depression, and that lycopene treatment alleviates this inhibition.
The study “offers an effective avenue for the development of novel antidepressant therapies,” the authors wrote. “We plan to conduct further verification in future studies and include multiple brain regions in our research.”
The pleasure we get from eating junk food — the dopamine rush from crunching down on salty, greasy chips and a luscious burger — is often blamed as the cause of overeating and rising obesity rates in our society. But a new study suggests that pleasure in eating, even eating junk food, is key for maintaining a healthy weight in a society that abounds with cheap, high-fat food.
Paradoxically, anecdotal evidence suggests that people with obesity may take less pleasure in eating than those of normal weight. Brain scans of obese individuals show reduced activity in pleasure-related brain regions when presented with food, a pattern also observed in animal studies.
Now, University of California, Berkeley, researchers have identified a possible underlying cause of this phenomenon — a decline in neurotensin, a brain peptide that interacts with the dopamine network — and a potential strategy to restore pleasure in eating in a way that helps reduce overall consumption.
The study, published in Nature, reveals an unsuspected brain mechanism that explains why a chronic high-fat diet can reduce the desire for high-fat, sugary foods, even when these foods remain easily accessible. The researchers propose that this lack of desire in obese individuals is due to a loss of pleasure in eating caused by long-term consumption of high-calorie foods. Losing this pleasure may actually contribute to the progression of obesity.
“A natural inclination toward junk food is not inherently bad — but losing it could further exacerbate obesity,” said Stephan Lammel, a UC Berkeley professor in the Department of Neuroscience and a member of the Helen Wills Neuroscience Institute.
The researchers found that this effect is driven by a reduction in neurotensin in a specific brain region that connects to the dopamine network. Importantly, they demonstrate that restoring neurotensin levels — either through dietary changes or genetic manipulations that enhance neurotensin production — can reinstate the pleasure in eating and promote weight loss.
“A high-fat diet changes the brain, leading to lower neurotensin levels, which in turn alters how we eat and respond to these foods,” Lammel said. “We found a way to restore the desire for high-calorie foods, which may actually help with weight management.”
While findings in mice don’t always translate directly to humans, this discovery could open new avenues for addressing obesity by restoring food-related pleasure and breaking unhealthy eating patterns.
“Imagine eating an amazing dessert at a great restaurant in Paris — you experience a burst of dopamine and happiness,” said Neta Gazit Shimoni, a UC Berkeley postdoctoral fellow. “We found that this same feeling occurs in mice on a normal diet, but is missing in those on a high-fat diet. They may keep eating out of habit or boredom, rather than genuine enjoyment.”
Gazit Shimoni and former UC Berkeley graduate student Amanda Tose are co-first authors, and Lammel is senior author of the study, which will be published March 26 in the journal Nature.
Solving a long-standing puzzle in obesity research
For decades, doctors and researchers have struggled to understand and treat obesity, as countless fad diets and eating regimens have failed to produce long-term results. The recent success of GLP-1 agonists like Ozempic, which curb appetite by increasing feelings of fullness, stands out among many failed approaches.
Lammel studies brain circuits, particularly the dopamine network, which plays a crucial role in reward and motivation. Dopamine is often associated with pleasure, reinforcing our desire to seek rewarding experiences, such as consuming high-calorie foods.
While raising mice on a high-fat diet, Gazit Shimoni noticed a striking paradox: While in their home cages, these mice strongly preferred high-fat chow, which contained 60% fat, over normal chow with only 4% fat, leading them to gain excessive weight. However, when they were taken out of their home cages and given free access to high-calorie treats such as butter, peanut butter, jelly or chocolate, they showed much less desire to indulge than normal-diet mice, which immediately ate everything they were offered.
“If you give a normal, regular-diet mouse the chance, they will immediately eat these foods,” Gazit Shimoni said. “We only see this paradoxical attenuation of feeding motivation happening in mice on a high-fat diet.”
She discovered that this effect had been reported in past studies, but no one had followed up to find out why, and how the effect connects to the obesity phenotype observed in these mice.
To investigate this phenomenon, Lammel and his team used optogenetics, a technique that allows scientists to control brain circuits with light. They found that in normal-diet mice, stimulating a brain circuit that connects to the dopamine network increased their desire to eat high-calorie foods, but in obese mice, the same stimulation had no effect, suggesting that something must have changed.
The reason, they discovered, was that neurotensin was reduced so much in obese mice that it prevented dopamine from triggering the usual pleasure response to high-calorie foods.
“Neurotensin is this missing link,” Lammel said. “Normally, it enhances dopamine activity to drive reward and motivation. But in high-fat diet mice, neurotensin is downregulated, and they lose the strong desire to consume high-calorie foods — even when easily available.”
The researchers then tested ways to restore neurotensin levels. When obese mice were switched back to a normal diet for two weeks, their neurotensin levels returned to normal, dopamine function was restored, and they regained interest in high-calorie foods.
When neurotensin levels were artificially restored using a genetic approach, the mice not only lost weight, but also showed reduced anxiety and improved mobility. Their feeding behaviour also normalised, with increased motivation for high-calorie foods and a simultaneous reduction of their total food consumption in their home cages.
“Bringing back neurotensin seems to be very, very critical for preventing the loss of desire to consume high-calorie foods,” Lammel said. “It doesn’t make you immune to getting obese again, but it would help to control eating behaviour, to bring it back to normal.”
Toward more precise treatments for obesity
Although directly administering neurotensin could theoretically restore feeding motivation in obese individuals, neurotensin acts on many brain areas, raising the risk of unwanted side effects. To overcome this, the researchers used gene sequencing, a technique that allowed them to identify specific genes and molecular pathways that regulate neurotensin function in obese mice.
This discovery provides crucial molecular targets for future obesity treatments, paving the way for more precise therapies that could selectively enhance neurotensin function without broad systemic effects.
“We now have the full genetic profile of these neurons and how they change with high-fat diets,” Lammel said. “The next step is to explore pathways upstream and downstream of neurotensin to find precise therapeutic targets.”
Lammel and Gazit Shimoni plan to expand their research to explore neurotensin’s role beyond obesity, investigating its involvement in diabetes and eating disorders.
“The bigger question is whether these systems interact across different conditions,” Gazit Shimoni said. “How does starvation affect dopamine circuits? What happens in eating disorders? These are the questions we’re looking at next.”
