A mechanism by which immune cells regulate obesity discovered

Researchers from the National Center for Cardiovascular Research have discovered a mechanism that can lead to treatments to regulate obesity, overweight, and for some associated pathologies such as fatty liver or type 2 diabetes.

The key is in macrophages, cells of the immune system that, in addition to being essential in the early response to infections, play a fundamental role in the proper functioning of our tissues and the regulation of obesity. Now, they explain how this regulation occurs in a work published in Nature Metabolism.

The study explains how the activation of the mitochondrial metabolism of macrophages that occurs in response to oxidative stress generated by excess nutrients contributes to the inflammation of adipose tissue and obesity.

«In recent decades, various studies have shown that, under normal conditions, macrophages in adipose tissue provide an anti-inflammatory and restorative environment, helping to deactivate any process that alters the normal function of this tissue; These macrophages are known as anti-inflammatories or «Type M2», Explain José Antonio Enríquez, study coordinator. However, in certain situations, he adds, ” macrophages M2 they interpret stress signals, which would normally appear in response to an infection, and promote inflammation as a defensive mechanism.

The results could be used to design new treatments for obesity and overweight and for some associated pathologies such as fatty liver or type 2 diabetes

These inflammatory processes originated by macrophages, Enriquez affirms, are responsible for the appearance of alterations that affect adipose tissue and “are at the origin of obesity and the metabolic syndrome associated with cardiovascular disorders, fatty liver or type 2 diabetes.”

Thus, as a response to the excess of nutrients generated by a diet high in fat, “macrophages change their function and promote inflammatory processes, forming pro-inflammatory macrophages of the ‘M1 type”.

Research now published has looked at how metabolic changes in macrophages regulate this inflammatory process that underlies obesity and metabolic syndrome. The new findings, he notes Rebeca Acín-Pérez, currently at UCLA, «reveal how the detection of oxidative danger signals, known as reactive oxygen species, by macrophages, induces changes in the mitochondrial metabolism of these immune cells that are necessary for their differentiation into a pro-inflammatory type M1.

This oxidative stress – he clarifies – is present in patients with morbid obesity and seems to be related to the high-fat diet, frequent in the inadequate western diet ».

Equipment – Cnic

One of the concussions of this study, ensures another of the directors of the work, David Sancho, is that it shows that, if said oxidative stress is reduced, “some of the harmful parameters associated with obesity are attenuated.”

In previous studies, CNIC scientists had found that the Fgr protein is key to regulating the activity of one of the complexes of the mitochondrial electron transport chain, complex II, in response to this oxidative stress, and favoring the generation of signals (cytokines and metabolites) that promote the immune response.

Although inflammation is a normal response of the body and beneficial to face aggressions when it is acute and transitory, it is very harmful when it becomes persistent or chronic, even if it is of low degree. This, the researchers explain, occurs in obesity and metabolic syndrome, and leads to increased cardiovascular mortality or the onset of diabetes.

The information provided by this new work shows that, in the absence of the Fgr protein, the liver increases its ability to eliminate fat, generating ketone bodies (chemical compounds produced by ketogenesis, a process by which body fat is used as a source. of energy) that are eliminated through the urine, and also improving the alterations that obesity causes in glucose metabolism (type 2 diabetes).

The results, obtained in mice, have been corroborated in human cohorts where the authors have found a strong correlation between the expression of Fgr and the negative effects derived from obesity.

Use specific inhibitors of the Fgr protein as a treatment for obese patients and / or patients with metabolic syndrome, with the aim of reducing associated inflammation and thus improving the parameters associated with these pathologies

The researchers conclude that their data suggest the possibility of using specific inhibitors of the Fgr protein as a treatment for obese patients and / or those with metabolic syndrome, with the aim of reducing the associated inflammation and thus improving the parameters associated with these pathologies, such as fatty liver or type 2 diabetes, thus helping to increase your life expectancy and quality.

Obesity is one of the main health problems as it is implicated in the development of heart diseases, strokes, cancer, liver steatosis, metabolic syndromes, high blood pressure, and some autoimmune diseases.

A combination of excessive nutrient intake, lack of physical activity, and genetic risk factors leads to an imbalance in energy demand versus energy consumed that initiates obesity.

Only in Spain, it is estimated that, in just over a decade, by 2030, there will be 27 million adults, 80% men and 55% women, with obesity or overweight problems.

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