🍽️ After 60 years of mystery, an obesity paradox solved

For sixty years, scientists believed the main role of an enzyme, called HSL, was to release stored fats. But a paradox emerged: people born without this enzyme see their fat mass decrease, not increase. This biological enigma has just been solved by Professor Langin and his team.

Fat cells, or adipocytes, are not simple inactive reservoirs. They contain structures, lipid droplets, where fats are stored until they are used. When the body needs energy, for example between meals, it activates the HSL protein. This acts like a key to unlock these reserves. This enzyme primarily responds to adrenaline, a hormone released during fasting or stress situations, which triggers the release of fatty acids to fuel the organs.


The surprise came from studying people and mice born without the gene producing HSL. Contrary to what one might think, this absence does not cause an accumulation of fat, but rather a reduction in adipose tissue, a medical condition called lipodystrophy. This observation contrary to the theory forced researchers to reconsider the functioning of this enzyme. Whether fat cells are defective because they are in excess (as in obesity) or in deficiency (as in lipodystrophy), they lead to similar metabolic disorders, harmful to cardiovascular health.

The Toulouse research team made a major discovery by finding HSL in an unexpected location in the cell: its nucleus. While it was mainly known on the surface of fat droplets, this enzyme is also present in the cell's command center. Jérémy Dufau, co-author of the study, specifies that in the nucleus, HSL interacts with many other proteins to participate in a cellular maintenance program, essential for the proper functioning of adipose tissue.

The HSL regulation system proves to be very sophisticated. Adrenaline, which activates the enzyme on the surface of fat droplets, simultaneously causes it to exit the nucleus during fasting periods. Crucially, obese mice show an abnormally high concentration of HSL in the nucleus. Dominique Langin emphasizes that this dual location finally explains the mystery of fat loss observed in patients without HSL and opens new perspectives for understanding metabolic diseases like obesity and their complications.

Adipose tissue: much more than simple storage

Fatty tissue is a true organ, capable of producing and secreting numerous hormones and signaling molecules, called adipokines. These substances directly influence appetite, how the body reacts to insulin, and the level of inflammation in the body.

There are different types of fat cells. White adipocytes, the most numerous, store energy. Brown adipocytes, on the other hand, burn calories to produce heat. This cellular diversity allows for fine regulation of our energy balance and our temperature.

The location of body fat is also very important for health. The accumulation of fat in the abdominal area is particularly associated with metabolic complications, while fat located on the hips and thighs presents fewer risks.

Fatty tissue also has a remarkable capacity for expansion. In case of prolonged excess, existing fat cells enlarge and new cells can form from specialized stem cells, a process called adipogenesis.