THEThe fight against obesity is a battle that millions of people face every day, often with an outcome that seems to get out of hand: the lost weight returns. This phenomenon, known as “yo-yo” effect, it is not just a question of will or discipline, but hides complex biological mechanisms. New research published in Nature reveals a surprising aspect of this difficulty.
Adipose tissue preserves an “epigenetic memory” of obesity, a molecular trace that persists even after significant weight loss, influencing the behavior of cells and predisposing the body to regain the lost kilos.
Obesity, fat returns: the study on epigenetic memory
The researchers, led by Nutritional Epigenetics laboratory at ETH Zurichaddressed this complex question through a study combining analyzes of human samples and animal models. In particular, they analyzed the adipose tissue of obese people before and after bariatric surgery.
Yo yo effect
The researchers observed that, despite the reduction in body weight, some genetic and transcriptional alterations persist. To delve deeper, they conducted experiments on mice, first feeding them high-fat diets to induce obesity and then switching them back to a normal diet to promote weight loss.
With advanced sequencing techniques and epigenetic analyses, they demonstrated that molecular changes in fat cells do not fully normalize even after returning to a healthy weight.
Obesity leaves a molecular “scar”.
One of the most interesting aspects that emerged from the study is that i key genes related to metabolismsuch as IGF1 and LPIN1, continue to show signs of deregulation even after significant weight loss. This suggests that obesity is not just a temporary condition but leaves a sort of molecular “scar”.
In mice, this epigenetic memory manifests itself through modifications in DNA and histones, the structural proteins of DNA. Some promoters of genes important for adipocyte function remain in an altered state, contributing to inefficient metabolism and a greater propensity to accumulate fat in response to new exposures to a calorie-rich diet.
Why does fat return after the diet?
The consequences of these discoveries are significant. It’s not just about explaining why so many people regain weight after a successful diet, but also about understanding how this epigenetic memory influences other metabolic functions, such as insulin sensitivity and glucose tolerance. The adipose tissue of a former obese person, in other words, never returns completely to normal, maintaining a sort of pathological predisposition.
The limitations of the obesity study
The clinical implications are important, but the study also has some limitations. For example, the human data comes from patients undergoing bariatric surgery, a drastic procedure that can affect the results of those who lose weight through diet and exercise. Furthermore, direct epigenetic analyzes on human adipose tissue have not been possible due to technical constraints, which leaves open the question of how applicable the results obtained in mice are to humans.
Reset the epigenetic memory of obesity?
Despite these limitations, the discovery of an epigenetic memory of obesity could open new avenues for the treatment and management of body weight. If it were possible to “reset” this molecular memory, it could not only improve the ability to maintain lost weight, but also prevent many of the complications associated with obesity. Targeted therapies, such as epigenetic interventions, could in the future offer more lasting solutions than current diet- and drug-based strategies.
The technologies available today
This study, however, represents only a first step. The technologies available today, such as GLP-1 receptor agonistsoffer new possibilities for weight management, but do not seem sufficient to eliminate the molecular traces left by obesity.
The positive effects of drugs such as semaglutidefor example, tend to fade once treatment is stopped, suggesting that the underlying problem remains unresolved.
Obesity: not just a question of diet and calories
Ultimately, obesity cannot be considered just a question of calories ingested and consumed. It is a condition that leaves deep marks, engraved in the adipose tissue and in the DNA itself, and these marks play a crucial role in the predisposition to regain weight. Understanding and addressing this epigenetic memory represents the next big challenge in the fight against obesity.
The Sources
Zimmet, P., et al. “Global and societal implications of the diabetes epidemic.” Nature (2001).
Who are the authors
Gianluca Pistore
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