Our fat cells, known as adipocytes, do far more than store extra body weight. They serve as an important energy reserve for the body. Inside each adipocyte, fat is packed into lipid droplets that can be tapped when fuel is needed -- for example, during the hours between meals. To release this stored energy, the body relies on a protein called HSL, which functions much like a switch. When energy is running low, hormones such as adrenaline activate HSL, prompting it to free fat that can then supply various organs.

Without HSL, it would be reasonable to expect fat to build up, as though the body had lost access to its energy supply. Surprisingly, this is not what happens. Research involving both mice and patients with mutations in the HSL gene shows that the lack of this protein does not lead to excess fat or obesity. Instead, affected individuals experience a loss of fat mass, a condition known as lipodystrophy.

Although obesity and lipodystrophy appear to be complete opposites, both involve fat cells that do not function properly. As a result, each condition can contribute to metabolic disturbances and cardiovascular problems.

HSL Found in an Unexpected Location Inside Fat Cells

To understand this surprising behavior, a team led by Dominique Langin, professor at the University of Toulouse within the I2MC, took a closer look at where HSL is found inside adipocytes. The protein is well known for its role at the surface of lipid droplets, where it helps break down stored fat. However, the study revealed that HSL also resides inside 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 completed his doctoral thesis on this topic.

The researchers also found that nuclear HSL levels are tightly controlled. Adrenaline, which activates the form of HSL located on lipid droplets, also encourages the protein to leave the nucleus. This process occurs naturally during fasting. In contrast, obese mice show elevated levels of HSL within the nucleus, suggesting a shift in this regulatory system.

A Revised Understanding of HSL's Role in Metabolism

"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," says Dominique Langin. This additional responsibility helps explain why the absence of HSL results in lipodystrophy, and it offers new insights into metabolic disorders such as obesity and related health complications.

This discovery appears at a critical time. In France, one in two adults is overweight or obese, and globally the number reaches two and a half billion people. Obesity increases the risk of a range of diseases, including diabetes and heart problems, and often reduces overall quality of life. Continued scientific research is crucial to improving prevention efforts and patient care.

Read more …New obesity discovery rewrites decades of fat metabolism science

Cancer biology, drug safety studies and aging research may all benefit from a fluorescent sensor created at Utrecht University. The new technology gives scientists the ability to watch DNA damage and repair unfold inside living cells in real time. This development, described in Nature Communications, enables types of experiments that were not previously possible.

DNA in our cells faces continual harm from sunlight, chemicals, radiation and even the normal processes that keep the body functioning. Most of this damage is corrected very quickly. When these repairs fail, the resulting errors can play a role in aging, cancer and several other diseases.

For years, researchers struggled to directly observe these repair events as they occurred. Many traditional approaches required killing and preserving cells at different time points, producing only isolated snapshots instead of a continuous view.

A New DNA Damage Sensor for Living Cells

Scientists at Utrecht University have now introduced a sensor that changes this situation. Their tool allows researchers to watch damage appear and fade inside living cells and also inside living organisms. According to the study published in Nature Communications, this capability opens the way to experiments that were previously out of reach.

Lead researcher Tuncay Baubec describes the approach as a method for looking inside a cell "without disrupting the cell." He notes that common tools such as antibodies and nanobodies often bind too tightly to DNA, which can interfere with the cell's own repair systems.

"Our sensor is different," he says. "It's built from parts taken from a natural protein that the cell already uses. It goes on and off the damage site by itself, so what we see is the genuine behavior of the cell."

How the Fluorescent Sensor Works

The system relies on a fluorescent tag attached to a small domain taken from one of the cell's own proteins. This domain briefly recognizes a marker that appears only on damaged DNA. Because the interaction is gentle and reversible, the sensor highlights the affected region while leaving the cell's repair work untouched.

Biologist Richard Cardoso Da Silva, who helped design and evaluate the tool, recalls the moment he recognized its potential. "I was testing some drugs and saw the sensor lighting up exactly where commercial antibodies did," he says. "That was the moment I thought: this is going to work."

A Continuous View of DNA Repair

The contrast with older methods is striking. Instead of running many separate experiments to capture different moments, researchers can now watch the entire repair sequence as a single continuous movie. They can track when the damage appears, observe how rapidly repair proteins arrive and see when the cell resolves the issue. "You get more data, higher resolution and, importantly, a more realistic picture of what actually happens inside a living cell," says Cardoso Da Silva.

The research team also tested the sensor outside the lab dish. Collaborators at Utrecht University used the tool in the worm C. elegans, a widely used model organism. The sensor performed equally well and revealed programmed DNA breaks that occur during the worm's development. For Baubec, this demonstration was essential. "It showed that the tool is not only for cells in the lab. It can be used as well in real living organisms."

The potential applications extend beyond watching repair occur. The sensor's protein domain can be connected to other molecular components, allowing scientists to map the locations of DNA damage across the genome or determine which proteins gather around a damaged region. Researchers can also reposition damaged DNA inside the nucleus to test how its location influences repair. "Depending on your creativity and your question, you can use this tool in many ways," says Cardoso Da Silva.

Better Tools for Medical and Drug Research

Although the sensor is not a treatment, it could significantly improve medical research. Many cancer therapies work by inflicting deliberate DNA damage on tumor cells, and early drug development often requires precise measurements of how much damage a compound creates.

"Right now, clinical researchers often use antibodies to assess this," Baubec says. "Our tool could make these tests cheaper, faster and more accurate." The team also sees potential uses in clinical settings, such as studying natural aging or detecting exposure to radiation or other mutagenic factors.

The innovation is already attracting interest. Several laboratories contacted the team before publication, eager to use the sensor in their own repair studies. To support this demand, the researchers have made the tool available without restrictions. Baubec notes, "Everything is online. Scientists can use it immediately."

Read more …Scientists capture stunning real-time images of DNA damage and repair

More Articles …