Scientists Uncover an Unexpected Role of the 'Fat-Burning Enzyme' After 60 Years of Research 0 11

An international group of researchers from the University of Toulouse has reported a solution to a long-standing scientific mystery related to the enzyme hormone-sensitive lipase (HSL). For about 60 years, it has been believed that this protein is solely responsible for breaking down fat in the body. However, new research has shown that its functions are much broader and involve fundamental mechanisms of adipose tissue function, according to SciTechDaily.

Since the discovery of HSL in the 1960s, scientists have considered it one of the key enzymes that trigger fat "burning." When needed, the body activates hormones, such as adrenaline, that turn on HSL. It helps break down triglycerides in fat cells and release fatty acids used as an energy source.

However, there remained a strange inconsistency: people and animals lacking HSL do not gain excess weight. On the contrary, they develop lipodystrophy—a rare condition in which adipose tissue disappears. The consequences can be similar to obesity: insulin resistance, diabetes, fatty liver disease, and cardiovascular disorders.

This paradox prompted scientists to reconsider the role of the enzyme.

Using modern imaging and molecular analysis techniques, researchers discovered that HSL operates not only on the surface of fat droplets, as previously thought. It also penetrates the nucleus of fat cells—a structure that governs gene function.

Inside the nucleus, HSL interacts with proteins that regulate gene expression and is involved in processes related to mitochondrial function and the structure of the extracellular matrix. These mechanisms are responsible for the health and normal functioning of adipose tissue.

According to one of the study's authors, Jérémie Dufau, in the nucleus of fat cells, HSL participates in maintaining the "program" that ensures the normal state and viability of adipocytes. The study showed that the behavior of HSL depends on the state of the body. During fasting or physical activity, hormonal signals move the enzyme from the nucleus to fat droplets, where it helps release energy.

In obesity, on the contrary, there is an accumulation of HSL in the nucleus of fat cells. Scientists suggest that this imbalance may be linked to metabolic disturbances and a deterioration of adipose tissue health. The authors emphasize that modern views on fat have significantly changed. Adipose tissue is now considered a full-fledged organ involved in hormonal regulation, inflammatory processes, and metabolism.

When the function of fat cells is disrupted, the consequences affect the entire body. In the case of obesity, cells enlarge, become inflamed, and lose the ability to manage energy properly. In lipodystrophy, on the other hand, the body cannot safely store lipids, leading to their accumulation in the liver and muscles.

The new study also revealed a possible interaction between HSL and the protein SMAD3, which is involved in the TGF-β signaling pathway. This pathway is associated with the development of fibrosis, insulin resistance, and obesity. Scientists believe that HSL may be a key element linking fat accumulation, inflammation, and metabolic disturbances.

According to the CDC, more than 40% of adults in the U.S. suffer from obesity.

Despite the popularity of GLP-1 group drugs, the biology of adipose tissue is still not fully understood.

The authors of the study believe that future therapy should focus not only on weight loss but also on restoring the normal function of fat cells.

In the editorial's opinion, the new research could significantly change the understanding of the nature of obesity and metabolic disorders. Scientists are increasingly concluding that the problem lies not only in the amount of fat but in the state of the adipose tissue itself and its ability to function properly as a vital organ of the body.