Is Obesity Reversible?

Obesity may affect the body differently at age 15 than it does at age 45. New research from Duke University School of Medicine suggests that adolescents retain a level of metabolic flexibility that is largely diminished by adulthood.

The study, published in the Journal of Clinical Investigation, found that although teenagers with obesity show early biological signs associated with metabolic disease, their bodies may still be able to adapt to the strain of excess weight. This resilience could make adolescence an especially important time for treatment.

By demonstrating that the biology of obesity changes with age, the findings point to a potential window in which obesity-related metabolic damage may be slowed, prevented, or possibly reversed before it becomes deeply established. John Rawls, Ph.D., a professor of molecular genetics and microbiology and member of the Duke Microbiome Center, said:

For a long time, medicine has tended to treat adolescents as little adults… But teenagers are still growing, building muscle and bone, and using energy in ways that are very different from adults. We wanted to understand how those differences shape obesity.

Why this research matters

Nearly one in five children in the United States has obesity. Without effective intervention, most children with obesity will continue to have obesity as adults, according to study co-author Sarah Armstrong, M.D., a pediatrician and medical weight management specialist at Duke Health.

The transition from adolescence to adulthood does not occur at exactly the same time for everyone. It generally takes place during the late teenage years and early 20s for women and during the early to mid-20s for men.

Researchers are now looking more closely at when the long-term health effects of obesity become biologically embedded. Understanding that timeline could help healthcare providers identify when treatment is most likely to alter a young person’s future health.

Teenagers’ gut microbiomes behave differently

The Duke research team examined two biological systems frequently connected to obesity: the microbiome and the metabolome. The gut microbiome is the community of bacteria and other microorganisms living within the digestive tract. The metabolome includes the chemicals produced as the body and its microbes break down food, generate energy, and carry out other essential processes.

Researchers first analyzed gut microbes collected from 287 teenagers participating in the Pediatric Obesity Microbiome and Metabolism Study. They confirmed that the microbiomes of adolescents with obesity differed in composition from those of teenagers at a healthy weight.

Jessica McCann, Ph.D., a senior research associate in molecular genetics and microbiology, then transplanted microbiome samples from adolescents with and without obesity into germ-free mice. In adult obesity research, transferring gut microbes associated with obesity can sometimes cause recipient mice to gain additional weight. That did not happen when the Duke researchers used microbiota collected from teenagers with obesity.

The result suggests that obesity-related changes in the microbiome are already beginning during adolescence, but those microbes may not yet be contributing to disease in the same way they often do in adults. Dr. McCann said:

This suggests there’s a developmental window in which the microbiome becomes involved in obesity… The relationship between the host and the microbiome may still be developing during adolescence, which means there may be an opportunity to change its trajectory.

In other words, the adolescent microbiome may be changing, but its relationship with the rest of the body has not necessarily become fixed. That could leave room for treatments that influence the microbiome before harmful patterns become more firmly established.

Early warning signs

Working with the Duke Molecular Physiology Institute, the research team also investigated how adolescents process nutrients. Adults with obesity frequently have elevated levels of branched-chain amino acids. They may also have higher levels of related substances called branched-chain keto acids, or BCKAs. Elevated BCKAs have been linked to insulin resistance and type 2 diabetes.

The adolescents in the Duke study displayed a different metabolic pattern. Their branched-chain amino acid levels were elevated, but their BCKA levels remained comparatively low.

The elevated amino acids may represent an early warning sign. However, the relatively low BCKA levels suggest that the teenagers’ bodies were still adapting to the metabolic pressure associated with excess weight. According to Dr. McCann,

The metabolome is showing early signs of disease progression, but it’s also showing evidence of adaptive plasticity.

This adaptive plasticity may help explain why obesity during adolescence is not biologically identical to obesity in adulthood. Teenagers’ bodies are still developing and may remain more capable of adjusting how they use and process nutrients.

A critical opportunity for obesity treatment

The findings strengthen the case for addressing obesity early rather than waiting until adulthood or until related conditions, such as insulin resistance, have fully developed. “The evidence increasingly supports intervening as early as possible,” said Dr. Armstrong, a professor of pediatrics at Duke.

During this period of metabolic flexibility, adolescents may be more responsive to weight-management strategies involving nutrition, physical activity, medication, or future microbiome-based therapies. The research does not suggest that one treatment will work for every teenager. Instead, it highlights the possibility that timing and individual biology may influence which approaches are most effective.

The study also challenges the idea that adolescent obesity should simply be managed using adult treatment models. Early biological warning signs do not necessarily mean that long-term metabolic disease is inevitable. By recognizing adolescence as a unique developmental stage, healthcare providers may have an important opportunity to intervene before temporary metabolic strain becomes a lasting health burden.

Your responses and feedback are welcome!

Source: “Study finds that obesity in adolescence may be more reversible than previously thought,” MedicalXPress, 8/24/26
Source: “Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy,” JCI, 7/15/26
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Opposite Signals Both Promote Weight Loss

Scientists have solved a puzzling question about a brain receptor involved in appetite: How can activating it and blocking it both lead to weight loss? The answer appears to depend on location.

In a study involving mice, researchers at the University of Cambridge found that drugs targeting the glucose-dependent insulinotropic polypeptide receptor, or GIPR, can influence body weight through separate regions of the brain. Activating the receptor in the brainstem reduced appetite, while blocking it in the hypothalamus strengthened the brain’s response to signals of fullness.

The findings, published in Nature Metabolism, could help explain why obesity medicines with seemingly contradictory mechanisms can produce similar outcomes. They may also point toward more effective combinations of GIPR-targeting treatments and drugs that act on the GLP-1 receptor, the target of medicines such as Wegovy and Ozempic.

As we know, substantial and sustained weight loss is often difficult to achieve through changes in diet and physical activity alone. Newer obesity medications work partly by influencing the biological systems that control hunger, fullness, and blood sugar.

Wegovy and Ozempic, for example, activate the glucagon-like peptide 1 receptor, commonly known as GLP-1R. Other treatments act on GLP-1R and GIPR at the same time.

That is where the scientific puzzle begins. Mounjaro and Zepbound activate GIPR as part of their mechanism. MariTide, an investigational medicine in phase 3 clinical trials, takes the opposite approach by blocking GIPR while activating GLP-1R. Both strategies can support weight loss, even though one turns the GIP receptor on and the other prevents it from working.

The Cambridge research suggests these approaches are not producing the same effect in the same place. Instead, they appear to engage distinct brain circuits that ultimately lead to reduced food intake and body weight.

To investigate, the researchers used genetically engineered mice in which GIPR had been removed from selected parts of the brain. Some mice lacked the receptor in the brainstem, an area near the spinal cord that helps regulate appetite and nausea. Others lacked it in the hypothalamus, which plays a central role in hunger, energy balance, and body-weight regulation. A third group of mice had not been genetically modified and served as a control.

The animals received different combinations of three types of treatment: a GIPR agonist that activated the receptor, a GIPR antagonist that blocked it, and a GLP-1-based drug. The researchers then measured how much the mice ate, how their body weight and fat mass changed, how well they regulated blood sugar, and which parts of their brains became active.

By comparing the results among the three groups, the scientists were able to identify the brain regions required for each treatment to work.

The experiments indicated that GIPR agonists depend largely on the brainstem. When the receptor was activated in this area, the mice ate less and lost weight. But when GIPR had been removed from the brainstem, the appetite-reducing effect was weakened, suggesting that this region is a key site of action for drugs that stimulate the receptor.

This helps explain how medicines that activate both GIPR and GLP-1R can influence eating behavior. Their effects are not limited to the digestive system or the pancreas; they also involve neural circuits that help determine when an animal stops eating.

GIPR antagonists worked differently. Their weight-loss effects depended more heavily on the hypothalamus. In this part of the brain, GIPR appears to act like a “brake,” reducing the strength of fullness signals coming from the brainstem.

Blocking the receptor releases that brake. As a result, signals telling the brain that the body has had enough food may become more powerful.

This means that activating and blocking GIPR can each reduce eating, but they reach that outcome through different routes. Activation directly engages appetite-suppressing pathways in the brainstem, while antagonism appears to make the hypothalamus more receptive to signals of satiety. That distinction may also explain why both strategies can complement GLP-1 medicines.

The findings offer a clearer biological explanation for the design of MariTide, which combines GIPR antagonism with GLP-1R activation. Because the two components may act through separate but interacting circuits, combining them could potentially produce a greater effect than targeting either pathway alone.

The researchers also found signs that GIPR antagonism could strengthen the effects of medicines aimed at the amylin receptor, another emerging target for obesity treatment. If that finding translates beyond mice, blocking GIPR might eventually be used to enhance several different types of weight-loss drugs — not only GLP-1 therapies.

Dr. Jo Lewis, the study’s first author from the Institute of Metabolic Science at the University of Cambridge, said:

Understanding which brain circuits respond to these medications — and how they do so — could help us design better drugs that produce more weight loss with fewer side effects, and which might work in combination with other obesity medicines to even greater effect…

Our work also strengthens the idea that the brain is central to obesity treatment. Obesity drugs are not acting simply on the gut or pancreas. Instead, they have important effects on specific, identifiable brain circuits that regulate appetite and food intake.

The research provides a useful framework for understanding an apparent contradiction in obesity pharmacology. Drugs that activate GIPR and drugs that block it are not necessarily cancelling out the same biological process. They may be acting in different brain regions, on different circuits and at different stages of the body’s appetite response.

However, the work was conducted in mice. Further research will be needed to determine how closely the same mechanisms apply to humans and whether targeting these pathways in combination can reliably improve weight loss, blood sugar control, or tolerability in patients.

Even so, the results underline an important shift in the science of obesity treatment. The effects of these medicines cannot be understood solely by studying the gut, insulin production, or digestion. Their success may depend just as much on where — and how — they alter communication within the brain.

Your responses and feedback are welcome!

Source: “Scientists solve the mystery of a brain “switch” that can trigger weight loss in opposite ways,” ScienceDirect, 8/15/26
Source: “Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism,” Nature Metabolism, 7/24/26
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Stigma and Association

Not long ago, an academic paper with several authors examined the existence and relationship of two concepts: weight stigma and weight stigma by association. The subjects were members of “a large, community-based sample.”

One objective was to rate parents on how caring and helpful they were willing to be, along with a rating to indicate how well they succeeded in that effort. When the results were tallied, it appeared that both obese parents and non-obese ones care equally for their children, be they daughters or sons. Furthermore, obese and non-obese parents are equally caring.

But: Obese parents are less effective, and parents of obese children are less effective.

One conclusion drawn by the researchers is that “Parents of children with obesity may experience weight stigma by association, which could have direct consequences for the parents, the children, and the parent-child relationship.” And, no matter how much they themselves weigh, parents of obese kids are rated as less effective. According to the authors of the paper,

There was also an effect of weight stigma wherein parents with obesity were also rated as less effective and helpful than parents without obesity.

Who is doing all this evaluating, and based on what standards?

It comes as no surprise to learn that a lot depends on who performs the evaluations. People who believe that parents are strictly and solely to blame for a child’s obesity do not care if those parents are themselves bulky or slender. The amount of censure is the same. And apparently, when either the young folks or their parents are obese, critics really don’t care how brilliant or talented the obese children in question may be. There is plenty of disapproval to go around.

One unfortunate result is that parents who are blamed and shamed “may internalize the negative parenting evaluations and subject themselves to further self-blame…,” which of course is exactly what their critics hope they will do. Even when parents exert themselves to make sure their methods “align with professional pediatric recommendations,” if their kids are overweight, those parents are still disrespected. The authors write,

One study found that parents who were stigmatized for their own weight reported greater use of restrictive feeding practices…

And yet, other research shows that when moms get strict about feeding, their kids are likely to eat more, not less. In effect, when an obese mama is picked on by someone who likes to stigmatize others, her kids will be even less carefully fed, and probably gain weight.

Another study dug deep and learned that when a girl is called “too fat” by a relative, her odds of being obese 10 years later increase by 62%. So maybe everyone should just pause and consider the many virtues of silence.

Several strengths

Characterized by its authors as possessing several strengths, this study is described as “the first randomized experiment to test weight stigma by association in a parent-child dyad using a large community sample.” Elaborate randomization standards are said to balance all potential variables and confounds across groups. It also involved large numbers of participants.

The authors note that their experimental stimuli “represented positive parenting practices” and
“used the same vignette of the parent-child dyad in all experimental conditions, which was crafted using the AAP parenting recommendations.” Summing up, they say,

Overall, the present randomized experimental study provides causal (rather than merely associative) evidence that weight stigma by association indeed occurs… Though a nascent area of research, weight stigma by association may have potential implications for parenting and effective pediatric obesity care.

Your responses and feedback are welcome!

Source: “Weight Stigma by Association Among Parents of Children with Obesity: A Randomized Trial,” ScienceDirect.com, 2022
Image by Tama66/Pixabay

Yale Study: Hunger Neurons in Weight Loss

For years, scientists believed that a group of brain cells known as agouti-related peptide, or AgRP, neurons played a straightforward role in metabolism: They stimulated hunger and resisted weight loss.

New research from Yale suggests the story is far more complicated.

In a study published in the Proceedings of the National Academy of Sciences (PNAS), researchers found that semaglutide, the active ingredient in Ozempic and other GLP-1 medications, appears to activate AgRP neurons rather than suppress them. Even more surprisingly, the study indicates that these hunger-promoting neurons may be necessary for maintaining the fat loss produced by the medication.

The findings challenge a long-standing assumption about the brain’s hunger circuitry and may help explain why newer GLP-1 therapies generate more substantial and lasting results than earlier weight-loss drugs.

Mateus d’Ávila, a Ph.D. candidate in neuroscience working in Tamas Horvath’s lab in the Department of Comparative Medicine at Yale School of Medicine (YSM) and first author of the study, said:

This completely changes how we think about the mechanism involved in these medications and provides new insight into the biology underlying their long-term effects, opening an avenue for the development of more efficient drugs.

The arrival of Ozempic and related GLP-1 therapies changed expectations, with some patients achieving sustained reductions of 10% to 15% of their body weight or more. Scientists know that these medications can reduce appetite and food intake. But appetite suppression alone may not fully account for their effectiveness.

Previous generations of weight-loss drugs could also substantially reduce hunger, yet they did not consistently produce the same degree of lasting weight loss as seen with semaglutide. That difference led the Yale team to suspect that GLP-1 medications were affecting additional biological systems.

One prominent theory held that the drugs worked partly by reducing the activity of AgRP neurons. Located in the brain’s hypothalamus, these neurons are strongly associated with hunger and feeding behavior. Because they encourage animals to seek and consume food, it seemed reasonable to assume that successful weight-loss treatments would need to inhibit them.

However, the role of AgRP neurons during long-term GLP-1 treatment had not been directly tested in a living organism. The Yale researchers set out to fill that gap.

Using a mouse model, the team combined several experimental approaches to examine what happened during semaglutide treatment. They tracked changes in body weight, food consumption, metabolism and energy expenditure.

The researchers also used genetic techniques to selectively remove or silence AgRP neurons. This allowed them to test whether the neurons merely responded to semaglutide or were actually required for the medication’s sustained effects.

The study results are striking. In mice genetically modified to lack AgRP neurons, GLP-1 treatment could initiate weight loss but could not sustain it. That suggested the neurons traditionally viewed as opponents of weight reduction were, in fact, helping preserve the drug’s long-term benefits.

Further investigations using electron microscopy, molecular biology and electrophysiology produced another unexpected finding: Semaglutide activated the AgRP neurons instead of inhibiting them. The researchers propose that this activation reflects the brain’s adaptation to the calorie deficit produced by GLP-1 treatment.

When calorie intake declines, AgRP neurons become more active as part of the body’s normal response to an energy shortage. Their best-known function is to increase hunger. The new study, however, suggests that their role is not limited to driving food intake. Under semaglutide treatment, the neurons may also participate in coordinating the loss of body fat.

In other words, the same neural system that signals a need for food may also help the body manage its energy stores during prolonged weight loss. This does not mean that hunger itself causes weight loss. Rather, it points to a previously unrecognized interaction between semaglutide, the brain’s response to calorie restriction, and the biological processes that determine whether lost weight stays off.

The discovery adds an important layer of complexity to scientists’ understanding of GLP-1 medications. Instead of simply shutting down the brain’s hunger signals, semaglutide may recruit parts of the hunger system and redirect their activity in ways that support sustained changes in body fat.

Because the study was conducted in mice, the results cannot yet be assumed to apply directly to humans. Researchers will need to determine whether the same neural mechanism operates in people taking semaglutide and other GLP-1 medications.

Still, identifying how the brain adapts during treatment could influence the next generation of obesity therapies. A more complete understanding of AgRP neurons might help scientists develop medications that preserve the benefits of GLP-1 drugs while improving their effectiveness, reducing unwanted effects, or helping a broader group of patients maintain weight loss.

d’Ávila said,

By identifying a previously unrecognized neural mechanism involved in sustaining weight loss, our work provides new biological insights that could eventually help researchers design therapies that are even more effective or have fewer side effects.

Your responses and feedback are welcome!

Source: “New study may change how we think about GLP-1s,” Yale News, 8/10/26
Source: “AgRP neurons are required for the weight-lowering effects of GLP-1 receptor agonists in female mice,” PNAS, 8/4/26
Image by denis1203.

Are GLP-1 Medications Replacing Bariatric Surgery?

The treatment landscape for obesity is changing rapidly, particularly among adolescents and young adults. New research suggests that GLP-1 medications have quickly become the most common medical treatment for younger people with obesity, while the use of metabolic and bariatric surgery has declined substantially.

A study published in JAMA Pediatrics found that the number of adolescents and young adults receiving GLP-1 medications increased sharply between 2022 and 2025-2026. During the same period, the proportion undergoing metabolic and bariatric surgery dropped significantly.

The findings offer a glimpse into how quickly obesity treatment has evolved as medications such as semaglutide have become more widely available. They also raise important questions about equitable access to treatment.

Researchers from the study examined real-world treatment patterns among more than 204,000 adolescents and young adults between the ages of 12 and 29 who received obesity treatment. The team compared treatment during two periods: May through November 2022, before semaglutide became widely available for adolescents with obesity, and June 2025 through January 2026, when GLP-1 medications were much more established in obesity care.

Researchers looked at whether patients received GLP-1 medications, metabolic and bariatric surgery, or both. They also examined differences related to age, sex, race and ethnicity, insurance status, and neighborhood socioeconomic conditions.

The results showed a striking change in how younger patients were treated. In 2022, 88.2% of patients receiving obesity treatment were treated exclusively with GLP-1 medications. By 2025-2026, that figure had risen to 96.1%. At the same time, the proportion of patients receiving metabolic and bariatric surgery declined from 11.6% to 3.7%.

Combination treatment remained uncommon. Only about 0.2% of patients received both GLP-1 medications and bariatric surgery during the study periods.

According to lead researcher Sarah Messiah, Ph.D., M.P.H., the study represents a major turning point in pediatric and young-adult obesity treatment. She said:

Our team’s study captures an inflection point in pediatric obesity treatment… While only a small proportion of adolescents and young adults currently receive both therapies, combination treatment was virtually nonexistent before GLP-1 medications became widely available. We’re now seeing clinicians integrate these therapies in different ways as obesity care continues to evolve.

Does this mean bariatric surgery is going away? Not necessarily.

The study does not establish that GLP-1 medications are superior to bariatric surgery, nor does it suggest that surgery is no longer an important treatment option. Instead, the findings demonstrate how the availability of highly effective medications has changed clinical practice.

Metabolic and bariatric surgery remains an established treatment option for some adolescents and young adults with severe obesity, particularly when other approaches have not produced sufficient results. GLP-1 medications offer another option that can be used without surgery, potentially changing how doctors and families approach treatment decisions.

For some patients, medication may be preferred because it avoids an operation. Others may benefit from surgical treatment based on their individual health needs, severity of obesity, response to previous treatments, and other medical considerations.

While the rapid growth of GLP-1 use is significant, the study also revealed disparities in who receives these medications. Older patients, patients with commercial insurance, and people living in higher-income neighborhoods were more likely to receive GLP-1 treatment.

Those differences suggest that simply having effective obesity medications available does not mean every patient has equal access to them. Insurance coverage, medication costs, healthcare availability, and socioeconomic circumstances can all influence whether a patient is able to receive treatment.

This is particularly important as obesity medications become a more prominent part of care for adolescents and young adults. If access remains concentrated among people with greater financial resources or more comprehensive insurance, existing health disparities could persist or widen.

For families navigating childhood or young-adult obesity, the research highlights how quickly treatment options are changing. Just a few years ago, bariatric surgery was one of the major medical interventions available for young people with severe obesity who needed more intensive treatment. Today, GLP-1 medications are increasingly becoming part of the conversation.

Your responses and feedback are welcome!

Source: “GLP-1 drugs are changing how teens and young adults treat obesity,” Consumer Affairs, 8/4/26
Source: “GLP-1 use rising rapidly among U.S. adolescents, young adults,” UT Southwestern Medical Center, 7/20/26
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