Unveiling the dual role of HSL protein in adipocytes

Our fat cells, called adipocytes, do more than just store extra weight. They play a key role in managing the body's energy. Adipocytes accumulate fat in the form of lipid droplets that the body can use when needed-for example, during fasting periods between meals. To do this, the body uses the HSL protein like a kind of switch. When energy is lacking, HSL is activated by hormones such as adrenaline and releases fat to fuel various organs.

In the absence of HSL, one might assume that the energy tap is shut off and that fat would inevitably accumulate. Paradoxically, however, studies in mice and in patients with mutations in the HSL gene show that this does not lead to obesity with excess fat. Quite the opposite happens: the absence of this protein causes a reduction in fat mass, a pathological condition known as lipodystrophy.

Obesity and lipodystrophy, though seemingly opposite, share a common point : in both cases, adipocytes malfunction, leading to similar metabolic and cardiovascular complications.

To understand this peculiarity, the research team led by Dominique Langin, professor at the University of Toulouse within the I2MC, noticed that HSL was located in an unexpected area. In adipocytes, the protein is known to be on the surface of lipid droplets, where it acts as an enzyme breaking down fat. But the study reveals that it is also present in the nucleus of fat cells. "In the nucleus of adipocytes, HSL is able to associate with many other proteins and take part in a program that maintains an optimal amount of adipose tissue and keeps adipocytes 'healthy'," explains Jérémy Dufau, co-author of the study, who defended his doctoral thesis on this subject.

Moreover, the study shows that the amount of HSL in the nucleus is finely regulated. Adrenaline, which activates the enzyme on the lipid droplet, also promotes its exit from the nucleus. This is what happens during fasting. In a pathological context, the amount of nuclear HSL is increased in obese mice.

HSL has been known since the 1960s as a fat-mobilizing enzyme. But we now know that it also plays an essential role in the nucleus of adipocytes, where it helps maintain healthy adipose tissue."

Dominique Langin

This new role explains the lipodystrophy observed in patients lacking HSL and opens avenues for a better understanding of metabolic diseases such as obesity and its complications.

This discovery comes at a timely moment. Overweight and obesity affect one in two adults in France. Worldwide, two and a half billion people are affected. Obesity increases the risk of many diseases, including diabetes and heart disease, and impairs quality of life. Continued research is essential to improve prevention and patient care.