MADRID.– Obesity leaves a deep mark on the body. So deep that Despite weight loss treatments or surgeries, the threat of fat regain is always there. And although the stigma surrounding the disease may lead one to think otherwise, science is beginning to illuminate that this is not a matter of will or lack of effort. The memory of this disease is written in the cells: research published this Monday in the journal Nature described, in mouse models and in human cells, a molecular mechanism in fatty tissue that predisposes us to gain weight after losing it. The authors suggest that this finding could help explain the yo-yo or rebound effect by which obese people gain weight again after bariatric surgery, for example.
This condition, which is characterized by an excessive accumulation of fat in the body and affects one in eight people in the world, is convoluted, complex and chronicforever. His signature and his legacy persist over time, even despite having undergone treatments or diets to lose weight. The scientific community had been suggesting for some time that there was a kind of metabolic memory that facilitates weight gain, but the mechanisms behind the long shadow left by the disease were not precisely known. Until now.
The study published today in Nature illuminates this path of research a little more and shows that Adipocytes, which are the cells of fatty tissue, retain a memory of obesity through epigenetic changes that persist even if weight has been lost.. “The discovery reveals a molecular mechanism in fat cells that predisposes them to regain weight more efficiently after being exposed to higher calorie consumption. It also highlights that the difficulty in maintaining weight loss after an intervention It is not simply a matter of lack of effort or willpower, but could be driven by an underlying biological phenomenon.“, summarizes Ferdinand von Meyenn, author of the study and researcher at the Federal Polytechnic School of Zurich.
Inside every cell, there is a manual for life: DNA. There, in that book with 3 billion chemical letters, are the instructions to make the human being function and the genes are like pages that store the specific recipes to make the proteins necessary to breathe, eat or sleep. In that context, the epigenome, which is made up of chemicals that stick to genes without modifying their sequence, would be like a kind of orthographic system that adds periods, commas and accents to refine the understanding of instructions. Thus, if an accent is added to a word or a comma is moved, the entire phrase can change its meaning.
Alterations in the epigenome prime the adipocyte to rapidly regain weight once high calorie intake resumesShutterstock – Shutterstock
The epigenome works like a switch, turning gene activity on or off. And what Von Meyenn’s team found is that, During obesity, very particular changes occur in the epigenome of fat cells, leaving genes on and off that should not be that way.. These modifications, the scientist explains in an email response, “prepare the adipocyte to quickly regain weight once high calorie intake resumes. Our research shows that some of these alterations persist after weight loss in specific genes or genomic regions. The epigenome of adipocytes previously exposed to obesity may be programmed to return to an obese state more quickly or more efficiently due to these changes.”
Due to the technical limitations to analyze the epigenome in humans, the researchers complemented their studies in human cells with experiments in animal models, explains Daniel Castellano, co-author of the study and postdoctoral researcher in the Oncomicrobiota Laboratory of the Clinical and Translational Research in Cancer group. from the Biomedical Research Institute of Malaga (Ibima). “The mouse gives us the opportunity to study the epigenome because we cannot do it in humans. In humans we can see which genes are working and which are not and we saw that there was a transcriptomic deregulation, genes turned on and off that should not be. And this deregulation persisted after losing weight,” he points out. Then, in mice, they also saw that this phenomenon with some genes turned off and on was “very similar” to what they had perceived in human cells and, after studying various epigenetic modifications, they confirmed that “this deregulation of genes was due, in a proportion elevated, to the epigenetic alterations that had remained after weight loss.”
Researchers do not know how long this memory of obesity identified in adipocytes lasts. Their findings showed that epigenetic changes persisted, at least up to two years in humans after weight loss surgery and up to eight weeks in mice, but there is no defined timeline, Von Meyenn admits: “The duration of this memory probably depends on the cellular renewal of the tissue. For example, adipocytes have a half-life of 10 years, after which the tissue is replenished with new cells.”
Castellano also clarifies that this molecular mechanism described would not explain 100% of the rebound effect. In fact, The research does not reveal a causality between the presence of this obesogenic memory and the yo-yo effect, but there is “a concordance. Mechanistically, we cannot prove that this rebound effect is due to changes in adipocytes, but we have found epigenetic alterations in several areas and we see that there is an overexpression of genes related to inflammation and the metabolism of the adipocyte itself. Functionally, it makes sense with what happens to fatty tissue in obesity,” he explains. Von Meyenn adds that adipocytes alone would not be the only ones responsible for the yo-yo effect. “This phenomenon of epigenetic memory can also exist in these other cells. “Other types of cells and organs, such as the brain (involved in controlling satiety and appetite), may also be involved.”
The researcher at the Federal Polytechnic School of Zurich affirms, however, that The study opens the door to the development of new strategies (pharmacological, dietary or other) to correct this epigenetic memory. “Currently, there are no pharmacological strategies to erase this memory. While some drugs used in cancer therapy target enzymes responsible for epigenetic changes, these approaches are global and do not focus on specific regions of the epigenome where lasting alterations might reside. There are emerging molecular strategies to induce changes in specific epigenetic regions, but they require further research and are not yet approved for use in humans. Once this phenomenon is better understood, possible strategies could include pharmacological interventions, dietary changes or the incorporation of functional foods,” he suggests.
Once the phenomenon observed in the study is better understood, possible strategies could include pharmacological interventions, changes in diet or incorporation of functional foods.IMEO – IMEO
Andreaa Ciudin, head of the Comprehensive Obesity Treatment Unit at the Vall d’Hebron Hospital in Barcelona and member of the board of directors of the Spanish Society for the Study of Obesity, describes this research, in which she did not participate, as “ interesting in the result, but worrying at the same time.” “This research opens a perspective of endless studies. Where there is DNA, there is epigenetics, because in the DNA chain there will always be factors that regulate its transcription. But It is difficult to explore epigenetics because it is very volatile and I don’t know how we could influence epigenetics chronically”, he proposes.
For his part, José Balibrea, head of Endocrine-Metabolic and Bariatric Surgery at Germans Trias i Pujol in Badalona, calls this study, in which he did not intervene, as “an important advance” to understand the importance of the obesogenic environment in the evolution of the disease. “The investigation reveals one of the key mechanisms to understand that obesity is a chronic disease with a tendency to relapse and that requires permanent treatment. What is not clear is whether we already have this predisposition before being obese or if, throughout the development of the disease, you generate that susceptibility and that memory,” he points out.
Speaking to the Science Media Center portal, José Ordovás, director of Nutrition and Genomics at Tufts University in Boston (USA), also highlights that, “although the findings are solid and supported by both human and animal data, “The study has limitations, including lack of direct epigenetic analysis in human samples, heterogeneity in human data sets, and lack of long-term follow-up in mice.” “It does not establish causality between epigenetic changes and weight recovery, so more research is required to confirm the mechanisms,” he says, although he admits that the implications of these findings in the real world are “significant: The study highlights the biological basis of weight regain, reduces stigma, and emphasizes the need for long-term supportive interventions. Opens avenues for targeted therapiessuch as medications or epigenetic editing, to ‘reset’ adipose tissue memory and improve weight loss maintenance. The personalized weight management strategies “They could be based on the genetic and epigenetic profile of an individual, while public health policies could prioritize prevention and early intervention to avoid the establishment of an obesogenic memory.”
By Jessica Mouzo
THE COUNTRYAccording to the criteria of
In what ways do you believe this study could reshape our understanding of the psychological barriers to sustained weight loss, beyond biological factors?
Ded questions to elicit thought-provoking responses from the interviewees:
1. Can you discuss the significance of this study in understanding the biological basis of weight regain after weight loss?
2. How do epigenetic changes in fat cells contribute to the yo-yo effect and persistent difficulty in maintaining weight loss?
3. Can you explain the implications of this study for personalized weight management strategies?
4. What role does environmental and lifestyle factors play in the development of obesogenic memory in adipocytes?
5. Are there potential pharmacological or dietary interventions that could target the epigenetic changes identified in this study to prevent weight regain?
6. How can healthcare professionals use these findings to better support patients in their weight loss journeys and improve long-term success rates?
7. Can you comment on the challenges faced by individuals in maintaining weight loss and the need for a multi-disciplinary approach to treatment?
8. As a bariatric surgeon, what is your perspective on the impact of this study on the management of obesity and its relapse?
9. What more research is needed to fully understand the mechanisms of obesogenic memory and its implications for public health policies?
10. Can you speculate on the potential long-term impact of this study on the development of targeted treatments and preventive strategies for obesity?
