Reasons for easy weight gain: Obesity has 'memory' and retains mechanisms in cells

Research reveals a molecular mechanism in fat tissue that makes people more likely to regain weight. The finding helps explain the 'yo-yo effect' in people trying to lose weight.

Obesity leaves a deep mark on the body. So deep that, despite treatments or surgery to lose weight, the threat of regaining it is ever-present. And while the stigma surrounding the disease might lead people to think otherwise, science is starting to make clear that it's not a matter of willpower or lack of effort. 'Memories' of obesity are recorded in cells: research in mouse models and in human cells, published on November 18 in the journal Nature, describes a molecular mechanism in fat tissue that makes people more likely to gain weight after losing it. The authors suggest that the finding could help explain the 'yo-yo effect', whereby obese people tend to regain weight when trying to lose it, such as through bariatric surgery (partial removal of the stomach) or dieting.

Science is starting to shed light on the fact that weight gain isn't a matter of willpower or lack of effort. (Photo: NurPhoto/Getty Images)

Obesity, characterised by excessive accumulation of body fat and affecting one in eight people worldwide, is a complex, puzzling and chronic condition. Its signs and 'legacies' persist over time, even after patients have undergone treatments or diets to lose weight. The scientific community has long assumed that there is a kind of metabolic memory that facilitates weight gain, but the mechanisms behind the long shadow the disease casts have remained largely unknown. Until now.

Research published in the journal Nature sheds further light on this research avenue and shows that adipocytes, which are cells of fat tissue, retain the memory of obesity through epigenetic changes that persist even after weight loss.

'This finding reveals a molecular mechanism in fat cells that makes us more likely 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 may be due to an underlying biological phenomenon,' explained Ferdinand von Meyenn, author of the study and a researcher at the Swiss Federal Institute of Technology in Zurich.

Mechanism of remembering "memories" of obesity

Inside every cell, there is a 'manual' that gives instructions for life, called DNA. There, in this book of three billion chemical letters, are the instructions for how humans function, and genes are like pages that record specific recipes for making the proteins needed to breathe, eat or sleep. In that context, the epigenome , made up of chemicals that attach to genes without changing their sequence, would be like a kind of 'spelling' system that adds periods, commas and accent marks to refine the understanding of the instructions. If you add an accent to a word or move a comma, the entire meaning of a sentence can change.

The epigenome acts like a switch, turning gene activity on and off. And Von Meyenn's team found that during obesity, very specific changes occur in the epigenome of fat cells, turning genes that shouldn't be on on and off (i.e. 'add a period, a comma' ).

These changes 'prepare the fat cell to rapidly regain weight when high calorie intake is resumed,' the scientist explained in an emailed response. 'Our study 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 an obese state more quickly or more efficiently due to these changes ,' he added.

Due to technical limitations in analyzing the human epigenome, scientists have supplemented their studies in human cells with experiments in animal models.

Fat tissue cells retain the memory of obesity through epigenetic changes that persist even after weight loss. (Photo: The Age).

"Mice give us the opportunity to study the epigenome because we can't do it in humans ," explains Daniel Castellano, co-author of the study, who works in the Clinical and Translational Oncology Research Group at the Institute of Biomedical Research of Málaga (IBIMA). "In humans, we can see which genes are active and which are not, and we see that there is transcriptional dysregulation, genes turning on and off that shouldn't be on. And this dysregulation persists after weight loss."

Then, in mice, the team also found that this phenomenon, where certain genes are turned on and off, was 'very similar' to what they saw in human cells. After studying some of the epigenetic changes, they discovered that ' this gene dysregulation was due to epigenetic changes that were maintained after weight loss.'

The researchers don't know how long the obesity memory identified 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's no clear timeline.

"The duration of this memory may depend on the tissue's cellular turnover," Von Meyenn admits. " For example, fat cells have a half-life of 10 years, after which the tissue is replenished with new cells."

Fat cells alone are not entirely responsible for the yo-yo effect, adds Von Meyenn. 'This epigenetic memory phenomenon may also exist in other cells. Other cell types and organs, such as the brain (which is involved in controlling satiety and appetite), may also be involved.'

Impacting epigenetic memory to aid weight loss

However, Von Meyenn added that this study opens the door to the development of new strategies (pharmacological, dietary, or other) to repair this epigenetic memory.

'Currently, there are no pharmacological strategies to erase this memory. Although some drugs used in cancer therapy target enzymes responsible for epigenetic changes, these approaches are global and do not target specific regions of the epigenome where lasting changes may occur. There are emerging molecular strategies to induce changes in specific epigenetic regions, but these require further study and are not yet approved for use in humans. Once the phenomenon is better understood, possible strategies may include pharmacological interventions, dietary changes or combinations of functional foods ,' he suggests.