Science Reveals Cause of Diet’s Yo-Yo Effect

According to a recent national survey, 63.7% of men and 48.4% of women in our country are overweight, while 19.3% of men and 18.0% of women are obese. If current trends continue, severe obesity is expected to affect 37% of the Spanish population by 2035.

The emergence of a new generation of anti-obesity drugs, GLP-1 receptor agonists, meant real revolution in the treatment of this disease. These drugs have also been shown to be much more effective because they also improve kidney function, reduce the risk of fatal cardiac events, and are associated with protection against neurodegeneration. In recent months, they have also been shown to help reduce pain associated with knee osteoarthritis and even reduce the risk of developing addictions such as alcoholism.

But, Even with the use of these drugs, regaining lost weight remains a variable that is difficult to control.

Overcoming this barrier to long-term treatment success is difficult because molecular mechanisms which underlie this phenomenon remain largely unknown.

From a genetic point of view, there are studies that show that hUp to 75% of changes in body mass index (BMI) can be explained by genetic factors. However, the regulation of body fat also depends on a number of factors, such as environmental, metabolic, neural, behavioral and endocrine influences. This is what science calls “epigenetics” and is what makes it so difficult to maintain your desired weight.

Memory of obesity

According to a new investigation carried out by the Federal Polytechnic School of Zurich (ETH) and in which researcher Daniel Castellano-Castillo from the Malaga Institute of Biomedical Research and Nanomedicine Platform (IBIMA) participated, adipose tissue will retain epigenetic memory of obesity after weight loss.

Work published this week in the magazine Nature, explains that This memory occurs because the experience of obesity leads to changes in the epigenome, a set of chemical tags that can be added or removed from cells’ DNA and proteins that help increase or decrease gene activity.

In case fat cells, The change in genetic activity appears to prevent them from performing their normal functions. This deterioration, as well as changes in genetic activity, They can persist long after the weight has dropped to a healthy level.

The researchers used adipose tissue cells from 18 non-obese people and another 20 before and after weight loss following bariatric surgery. Two years after the obese participants had weight-loss surgery, they had lost a large amount of weight, but the genetic activity of their fat cells still showed a pattern associated with obesity. The scientists found similar results in mice that lost a lot of weight.

In human and mouse fat cells, genes that are activated in obesity are involved in stimulate inflammation and fibrosis (formation of hard, scar tissue). Turned off genes help fat cells function normally. Studies conducted in mice have linked these changes in gene activity to epigenome changes, which has a powerful effect on the activity of a gene, including whether it is activated or not.

The scientists tested the sustainability of these changes by putting obese mice on a diet. Several months after the mice lost weight again, the changes in their epigenomes persisted. it is as if the cells “remember” that they were in an obese body.

“Our results indicate the existence obesity of memory, based mainly on stable epigenetic changes, in mouse adipocytes and possibly in other cell types,” the authors note. “These changes appear to prepare cells for pathological responses in an obesogenic environment, promoting the problematic yo-yo effect often seen with dieting. Taking these changes into account in the future may improve weight management and long-term health outcomes,” they add.