Anorexia Beyond the Mind: The Relationship Between Body Fat and the Origin of the Disease

For a long time, anorexia nervosa has been mainly explained through what happens in the brain: the fear of gaining weight, the altered perception of one's own body, the relationship with food, or the psychological mechanisms that lead to restricting food intake. However, there is increasing evidence that part of the explanation could also be found in the functioning of the rest of the body.

New research has found a link between anorexia and a gene involved in how our cells store fat, pointing to a biological process that, in principle, has little to do with body image or the emotions usually associated with this disorder.

The study, published on October 8 in Frontiers in Psychiatry, adds to a line of research that has been exploring the role of metabolism in anorexia for years. And although many questions remain unanswered, its results help to understand why this disease is much more complex than traditionally considered.

An unexpected connection with fat reserves

The focus of the research is a gene called PLIN4, responsible for producing a protein involved in fat storage within cells.

To understand its importance, it is necessary to remember that fat is not simply a reserve we accumulate when we consume more energy than we expend. It is also an essential component for the functioning of numerous bodily processes, from the production of certain hormones to the maintenance of cell membranes.

Some of these lipids are stored in small cellular structures known as lipid droplets, which function as reservoirs that allow fats to be conserved and used when the body needs them. The protein produced by PLIN4 is precisely found on their surface and participates in their organization.

What is striking is that this gene is mainly expressed in adipose and muscle tissue, while its presence in the brain is much lower. Hence the researchers' interest in finding out whether certain alterations in its function are related to anorexia nervosa.

To verify this, they analyzed the DNA of 154 people diagnosed with the disease, selected for characteristics such as significant family history, persistent difficulties with treatments, or unusual clinical manifestations.

The results revealed a considerable difference.

Genetic alterations almost four times more frequent

According to the published data, approximately 11% of the patients studied had rare variants of PLIN4 considered potentially harmful. In the reference population used for comparison, that proportion was 3.2%.

The alterations, therefore, appeared with an almost fourfold higher frequency among people with anorexia included in the study.

The scientists also found six patients with variants that could significantly affect the protein's function. In four of these cases, they identified relatives who shared the same alteration and had also developed anorexia, a finding that sparked special interest due to its possible relation to hereditary predisposition.

However, the fact that these variants appear more frequently does not mean they are solely responsible for causing the disease.

The research was conducted with a relatively small group selected for specific clinical characteristics, so it remains to be seen whether the same association is observed in other patients. Moreover, although the detected alterations are considered potentially harmful, it is still unknown how they actually affect cellular function.

Still, the results offer a concrete clue to study biological processes that have so far received less attention.

What is the relationship between these alterations and the development of anorexia?

One of the difficulties in studying anorexia is distinguishing which bodily changes existed before the disease and which appear as a consequence of malnutrition, since prolonged food restriction modifies metabolism, hormone production, and the way the body uses its energy reserves.

In this case, there is an important difference: the researchers have identified DNA variants that, when inherited, are present from conception. Therefore, they do not appear as a consequence of weight loss or the metabolic alterations caused by the disease.

This allows investigation into whether certain genetic characteristics influence the predisposition to develop anorexia. In fact, the fact that some of the variants found also appear in relatives with the same disorder reinforces the value of studying this possible relationship.

However, it has not yet been demonstrated that PLIN4 alterations actually modify the way cells store fat or contribute to the development of anorexia. What the scientists have found is a genetic association that they will now need to confirm and study in greater depth to understand whether it has consequences for the body's functioning.

The relationship between anorexia and metabolism is not new

Although the latest discovery has attracted attention due to its relation to body fat, the idea that anorexia has a metabolic dimension has been gaining ground among researchers for years.

In 2019, a large international study published in Nature Genetics analyzed genetic information from 16,992 people with anorexia nervosa and 55,525 control participants.

The results identified eight regions of the genome associated with a higher susceptibility to develop the disease. But the most interesting aspect was that some of these associations were not limited to psychiatric features: genetic links also appeared with aspects related to glucose regulation, lipids, and body composition.

Based on those results, the authors proposed considering anorexia as a disorder with both psychiatric and metabolic components.

This helps broaden the view of a disease that affects eating and weight but whose development involves mechanisms that are not yet fully understood.

The study published this October adds an additional piece to that knowledge. Instead of analyzing only large genetic associations, it points to a specific gene related to cellular fat storage, allowing for more focused research on its possible function.

Better understanding why anorexia appears

Anorexia nervosa remains one of the most severe and complex eating disorders, and its course varies greatly from person to person. Some go through prolonged processes, with relapses and medical complications, while others manage to recover completely. Understanding why these differences occur is also one of the challenges of research.

On that path, better knowledge of the genetic factors involved in the disease would help understand why some people are more vulnerable to developing it and, over time, find new ways to address it. If the relationship between PLIN4 and anorexia is confirmed, researchers will have a new biological mechanism to study, although it is still too early to know whether it will have therapeutic applications.

For now, treatment still requires medical attention, nutritional recovery, and psychological support. Research continues to advance on a disease with many questions yet to be answered, and better understanding what happens in the body is part of that work.