Research reveals a molecular mechanism in adipose tissue that makes it easier for individuals to regain weight. This discovery helps explain the “yo-yo effect” in those attempting to lose weight.
Obesity leaves a significant mark on the body. So profound that, despite treatments or surgeries for weight loss, the threat of regaining weight always looms. And while the stigma surrounding this condition may lead some to think otherwise, science is beginning to clarify the reality that this is not merely a matter of willpower or lack of effort. The “memory” of obesity is recorded in the cells: research on mouse models and human cells, published on November 18 in the journal Nature, describes a molecular mechanism in adipose tissue that predisposes individuals to regain weight after losing it. The authors suggest that this finding could help explain the “yo-yo effect,” whereby obese individuals are prone to regaining weight in their attempts to lose it, whether through bariatric surgery (removing part of the stomach) or various diets.
Science is beginning to clarify that weight gain is not simply a matter of willpower or lack of effort. (Photo: NurPhoto/Getty Images)
Obesity, characterized by excessive accumulation of fat in the body and affecting 1 in 8 people worldwide, is a complex, misunderstood, and chronic condition. Its signs and “legacy” persist over time, even when patients have undergone treatments or diets to lose weight. The scientific community has long believed that there exists a form of metabolic memory that facilitates weight gain, but the mechanisms behind the long shadow this condition casts have remained unclear until now.
The study published in Nature sheds more light on this research path and shows that fat cells, which are cells of adipose tissue, retain a memory of obesity through epigenetic changes that persist even after weight loss.
“This finding reveals a molecular mechanism in fat cells that makes it easier for us to regain weight after exposure to increased calorie intake. It also highlights that the difficulty in maintaining weight after intervention is not simply a matter of lack of effort or willpower, but could be due to an underlying biological phenomenon,” explained Ferdinand von Meyenn, the study’s author and a researcher at the Swiss Federal Institute of Technology in Zurich.
The Mechanism of “Obesity Memory”
Inside each cell lies a “handbook” guiding life, which is DNA. Within this book, containing three billion chemical letters, are instructions for how a person operates, with genes resembling pages that record specific formulas to produce the proteins necessary for breathing, eating, or sleeping. In this context, the epigenome, made up of chemicals that attach to genes without altering their sequence, acts like a “spell-check” system, adding punctuation and accents to refine the understanding of the instructions. Adding accents to a word or moving a comma can change the entire meaning of a sentence.
The epigenome functions like a switch, turning gene activity on and off. Von Meyenn’s team discovered that during obesity, very specific changes occur in the epigenome of fat cells, turning on and off genes that should not be activated (i.e., “adding punctuation.”).
The scientist explained in an email response that these changes “prepare fat cells to rapidly regain weight when high-calorie intake continues.” “Our research shows that some of these changes persist after weight loss in specific genes or gene regions. The epigenome of fat cells previously exposed to obesity may be programmed to return to a state of obesity more quickly or efficiently due to these changes,” he added.
Due to technical limitations in analyzing the epigenome in humans, the scientists supplemented their human cell studies with experiments on animal models.
Fat cells retain a memory of obesity through epigenetic changes that persist even after weight loss. (Photo: The Age).
Daniel Castellano, co-author of the study, working at the Clinical and Translational Cancer Research Group at the Málaga Biomedical Research Institute (IBIMA), explained: “Mice give us the opportunity to study the epigenome because we cannot do so in humans. In humans, we can see which genes are active and which are not, and we observe that there is a dysregulation of transcription, with genes activating and deactivating that should not be. And this dysregulation continues even after weight loss.”
Subsequently, in mice, the research team also found that this phenomenon, where some genes activate and deactivate, “closely resembles” what they observed in human cells. After examining several epigenetic alterations, they discovered that “this gene dysregulation is due to epigenetic changes that have been maintained after weight loss.”
The researchers are unsure how long the obesity memory defined in fat cells lasts. Their findings suggest that epigenetic changes persist for at least 2 years in humans after weight loss surgery and up to 8 weeks in mice, but there is no clear timeline.
Von Meyenn acknowledged: “The duration of this memory may depend on the turnover process of tissue cells. For example, fat cells have a half-life of 10 years, after which the tissue is replenished with new cells.”
Von Meyenn added that fat cells alone are not entirely responsible for the yo-yo effect. “This epigenetic memory phenomenon may also exist in other cells. Other types of cells and organs, such as the brain (involved in controlling feelings of satiety and appetite), could also be implicated.”
Impacting Epigenetic Memory to Aid Weight Loss
However, Von Meyenn further stated that this research opens the door for the development of new strategies (pharmaceutical, dietary, or other strategies) to rectify this epigenetic memory.
“Currently, there are no pharmacological strategies to erase this memory. Although some drugs used in cancer treatment target the enzymes responsible for these epigenetic changes, these approaches are global and do not focus on specific epigenetic regions where long-lasting changes may occur. Emerging molecular strategies aim to create changes in specific epigenetic regions, but these need further study and are not yet approved for human use. Once this phenomenon is better understood, feasible strategies may include pharmacological interventions, dietary changes, or combinations of functional foods,” he suggested.
