Since the 1960s, hormone-sensitive lipase (HSL) has been known as the enzyme that provides access to the energy stored in our fats. We might therefore think that its absence would cause obesity with excess fat mass. However, this is not the case, in fact the opposite occurs.
A team from the University of Toulouse and Inserm at the Institute of Metabolic and Cardiovascular Diseases (I2MC) resolved this paradox by showing that this protein also acts in an unexpected way in the nucleus of our fat cells, called adipocytes.
They are not only used to store excess pounds, but also play a key role in our body's energy management.
The role and dysfunction of adipocytes
Adipocytes accumulate fat in the form of lipid droplets that the body can use when needed, for example during periods of fasting between meals. To do this, it uses the HSL protein as a kind of switch. When the body lacks energy, it is activated by hormones like adrenaline and releases fat to provide fuel for various organs.
In the absence of the HSL protein, one might assume that the energy tap is turned off and fat will inexorably accumulate. However, paradoxically, we see in mice and in patients suffering from mutations in the gene encoding HSL that this does not lead to obesity with excess fat.
The opposite occurs: the absence of this protein causes a drop in fat mass, a pathological condition called lipodystrophy.
Obesity and lipodystrophy, although apparently opposite, share one thing in common: in both cases, adipocytes malfunction, leading to similar metabolic and cardiovascular complications.
To understand this singularity, the scientific team led by Dominique Langin, professor at the University of Toulouse within I2MC (Inserm/University of Toulouse), noticed that HSL was located in a previously unsuspected area. In adipocytes, the protein is known to be on the surface of the lipid droplet where it plays its role as a fat-cutting enzyme, but the study reveals that it is also in the nucleus of fat cells.
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Roles of HSL in adipocytes. HSL participates in the mobilization of fats stored in the lipid droplet. In the nucleus, it ensures the harmonious functioning of the adipocyte.
“ In the nucleus of adipocytes, HSL is able to associate with many other proteins and participate in a program that maintains an optimal amount of adipose tissue and 'healthy' adipocytes », Specifies Jérémy Dufau, co-author of the study and who defended his thesis on this subject.
Furthermore, the study shows that the amount of HSL in the nucleus is finely controlled. Adrenaline, which allows the activation of the enzyme on the lipid droplet, also promotes its exit from the nucleus. This is what happens during fasting. In a pathological context, the quantity of HSL in the nucleus is increased in obese mice.
2 billion people in the world are obese
“ HSL has been known since the 1960s as a fat-burning enzyme. But we now know that it also plays an essential role in the nucleus of adipocytes, where it participates in the maintenance of healthy adipose tissue. », concludes Dominique Langin. This new role could explain lipodystrophy in patients who do not have HSL and opens avenues to better understand metabolic diseases such as obesity and its complications.
This discovery comes at the right time. Overweight and obesity affect one in two adults in France. Globally, this concerns 2 and a half billion people. Obesity increases the risk of many diseases including diabetes and heart disease and affects quality of life. Continued research is essential to improve prevention and patient care.
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