Scientists identify brain area at origin of vicious circle that leads to weight gain

The abundance of foods rich in fat or sugar has led to more long-lived people, but it has also resulted in an epidemic of obesity-related diseases, placing strain on the resilience of health systems. One of the ways to curb this health crisis lies in the study of what happens in the brain when we are exposed to certain foods. A team led by Michiru Hirasawa, from Memorial University of Newfoundland in Canada, has recently published a paper in the journal PNAS in which they seek to understand the relationship between inflammation in the hypothalamus — a part of the brain that regulates energy balance and our sense of hunger — and the consumption of high-fat diets.

Science has long been aware that high-fat diets can lead to a vicious cycle that is difficult to stop. Such foods cause inflammation of the hypothalamus, which increases appetite to levels that cause us to eat more than we need and thus to gain weight. However, scientists have also observed a seemingly paradoxical effect: inflammation in that region of the brain is also associated with diseases such as anorexia and other weight-loss conditions. Hirasawa and his team used animal models to try to find out how this relationship between inflammation and a disordered appetite is regulated.

In their work, the researchers show that high-fat diets cause prostaglandin E2 (PGE2) — a molecule that regulates immune system processes such as fever — to activate the MHC hormone in the hypothalamus, which makes us feel hungry. This mechanism may also explain why brain inflammation sometimes leads to weight gain and, on other occasions, to excessive weight loss. If it is in a high concentration and produces intense inflammation, PGE2 suppresses appetite, but if the concentration is lower, it increases it.

The authors of the study found that by genetically modifying mice and eliminating the receptors for prostaglandin in the MHC neurons, the animals were protected against obesity or fatty liver caused by inflammation of the hypothalamus linked to a high-fat diet.

Hirasawa acknowledges that it is not easy to predict “the outcome of an inflammation, because low or high intensity is relative; it can be acute or chronic and involve many different organs, cells and molecules.” However, although they produce different ailments, “reducing inflammation can alleviate both symptoms.” As such, the researcher suggests that any strategy that achieves this effect can be useful from many points of view. “For example, the Mediterranean diet is anti-inflammatory and is known to help reduce weight in people who are overweight or obese.” Finally, he points out that it is also “essential to be selective with how and when anti-inflammatory treatments are used, as inflammation is also necessary for our daily functioning, for example, in healing wounds or fighting infections.”

At a time when some forecasts suggest that within less than a decade up to 80% of men and 55% of women in Spain will be overweight or obese, and when weight-loss drugs are becoming bestsellers, the possibility of finding therapeutic targets against uncontrolled appetite is of great scientific value. Hirasawa believes that his team’s findings “may one day lead to treatments for obesity.” Knowledge of the mechanism that starts with the ingestion of fatty foods and causes inflammation that increases appetite would allow the development of treatments to this end. The genetic modification to which the mice were subjected in the study published in PNAS seems a very radical option and it must be taken into account that PGE2 has many other functions, apart from inflaming the hypothalamus and making us hungry. “It is to be expected that treatments that block this mechanism will have an anti-obesity effect,” notes Hirasawa. However, he concludes: “It is critical to identify possible side effects and test their safety before using them.”

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