Spanish researchers have developed a therapy targeting macrophages, cells of the immune system, which opens the door to treatments against several diseases, including obesity.
- Obesity is generally defined by a body mass index (BMI) of 30 or more. A BMI between 25 and 30 is classified as overweight.
- Nearly one in two French people (47.3%) is overweight or obese, according to figures from the League against obesity in 2020.
- 17% of adults are obese, ie nearly 8.6 million people.
A new anti-obesity treatment could emerge after a major discovery by scientists. Spanish researchers have developed a new therapy that targets macrophages, immune cells present in all tissues whose role is to contribute to the maintenance and proper functioning of the latter and which are capable of regulating the metabolism of a person depending on the organ in which they reside. In experiments with mice, the compound they tested prevented the animals from gaining weight, despite eating a high-fat diet. The results of their new study have appeared in the journal Immunity on February 3, 2023.
A discovery that opens the door to many treatments
This treatment also prevented type 2 diabetes and fatty liver disease in mice. The Spanish research team says the discovery opens the door to better treatments for conditions linked to obesity and metabolic syndrome, such as cardiovascular disease. It also opens the door to a treatment for diabetes and certain cancers linked to excess weight.
Macrophages play an essential role in the early response to microbial infection. They are also linked to inflammation, a physiological response that helps repair damaged tissue. However, if the inflammatory response isn’t working properly, it can lead to chronic inflammation that triggers many conditions, including obesity, type 2 diabetes, and heart disease. Study leader Dr. David Sancho and his team discovered that macrophages adapt to the needs of the organ where they reside. This discovery “allows us to better understand how macrophages regulate their metabolism depending on the organ in which they reside”says Dr. Sancho in a Press release.
How could macrophages help treat obesity?
Macrophages are normally distributed throughout the body. They help clean the organs of all types of biological residues that need to be eliminated, such as harmful particles such as mineral crystals or viruses, or even dead cells. This study reveals for the first time that they are highly malleable.
“In tissues rich in extracellular fats and cholesterol, such as the lungs and spleen, macrophages adapt their metabolism to break down these fats through mitochondrial respiration”explains the first author of the study, Dr. Stefanie Wculek. “By using genetic or pharmacological methods to disrupt mitochondrial respiration, mitochondria can be eliminated from the lungs and spleen, while macrophages in other organs, which do not depend on mitochondrial respiration, survive.”
Transformation of macrophages into inflammatory cells
Another example is provided by macrophages located in body fat or adipose tissue. “Macrophages residing in the body fat of a normal-weight person are unaffected by mitochondria-disrupting treatments because their metabolism is less dependent on mitochondrial respiration. Indeed, fat cells, called adipocytes, are fully functional, leaving macrophages in a resting state”says Dr. Sancho.
“However, in obese people, excess fat exceeds the capacity of adipocytes and resident macrophages become activated, transforming into inflammatory cells that promote the development of insulin resistance, type 2 diabetes and hepatic steatosis”, adds the doctor. This modification of adipose tissue macrophages also makes them vulnerable. “Activated macrophages depend on mitochondrial respiration to process excess fat, which makes them vulnerable to therapeutic interventions, including pharmacological inhibitors of mitochondrial respiration.”
