Surprising obesity discovery rewrites decades of fat metabolism science

To release this stored energy, the body relies on a protein called HSL. This protein works like a switch. When energy levels drop, hormones like adrenaline activate HSL, triggering the release of fat that can be used by organs throughout the body.

Why Losing HSL Does Not Lead to Weight Gain

At first glance, it might seem logical that without HSL, fat would build up since the body would struggle to access its stored energy. However, research in mice and in people with mutations in the HSL gene shows a surprising outcome. Instead of gaining fat, these individuals actually lose it.

This loss of fat leads to a condition called lipodystrophy, where the body has too little fat tissue. Rather than causing obesity, the absence of HSL disrupts normal fat storage and results in reduced fat mass.

Obesity and Lipodystrophy Share Hidden Risks

Although obesity and lipodystrophy appear to be opposite conditions, they share an important similarity. In both cases, fat cells do not function properly. This dysfunction can lead to similar health problems, including metabolic issues and increased risk of cardiovascular disease.

A Surprising Discovery Inside Fat Cells

To better understand this unexpected behavior, researchers led by Dominique Langin at the University of Toulouse within the I2MC examined where HSL operates inside fat cells. Traditionally, HSL has been known to sit on the surface of lipid droplets, where it helps break down fat.

The new study revealed something unexpected. HSL is also found inside the nucleus of adipocytes, the part of the cell that controls gene activity. "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.

How HSL Moves Within the Cell

The researchers also discovered that the amount of HSL in the nucleus is carefully controlled. Adrenaline, which activates HSL to release fat, also signals the protein to leave the nucleus. This process occurs during fasting, when the body needs energy.

In contrast, studies in obese mice show higher levels of HSL remaining in the nucleus, suggesting that this balance may be disrupted in disease.

A New Role for a Well-Known Fat Enzyme

"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," concludes Dominique Langin.

This newly identified function helps explain why people lacking HSL develop lipodystrophy. It also opens new avenues for understanding metabolic diseases, including obesity and its complications.

Why This Discovery Matters Now

The timing of this discovery is significant. In France, one in two adults is overweight or obese. Globally, about two and a half billion people are affected. Obesity raises the risk of serious conditions such as diabetes and heart disease and can reduce quality of life.

Advances like this highlight the need for continued research to improve prevention strategies and develop better treatments for metabolic disorders.