But researchers uncovered something unexpected. HSL was not just working on the surface of fat droplets inside fat cells. It was also operating deep inside the nucleus of those cells, where DNA is stored and important genetic activity is controlled. The discovery revealed an entirely different side to a protein scientists had studied since the 1960s.

The findings, published in Cell Metabolism, helped solve a long-standing mystery in obesity research and opened new directions for understanding diabetes, heart disease, and other metabolic disorders.

Fat Cells Do Far More Than Store Calories

Fat cells, also called adipocytes, are often viewed as passive storage containers for excess calories. In reality, they are highly active cells that help regulate the body’s entire energy system.

Inside adipocytes, fat is stored in structures called lipid droplets. When the body needs fuel between meals or during fasting, hormones such as adrenaline trigger the release of that stored energy. HSL plays a central role in this process by breaking down triglycerides into fatty acids that other organs can use for fuel.

Scientists long assumed that removing HSL would prevent fat breakdown and lead to obesity. Surprisingly, that is not what happened.

Studies in both mice and people with mutations in the HSL gene showed the opposite effect. Instead of accumulating extra fat, they developed lipodystrophy, a rare condition in which the body loses healthy fat tissue.

That contradiction puzzled researchers for years.

Obesity and Dangerous Fat Loss Share Similar Problems

Although obesity and lipodystrophy seem completely different, they can produce many of the same health complications.

In obesity, fat tissue becomes enlarged and dysfunctional. In lipodystrophy, the body lacks enough properly functioning fat tissue. In both cases, adipocytes fail to regulate energy normally, which can contribute to insulin resistance, type 2 diabetes, fatty liver disease, inflammation, and cardiovascular problems.

This overlap suggested that healthy fat tissue is not simply about how much fat the body carries. The quality and function of fat cells may be just as important.

Researchers at the Institute of Cardiovascular and Metabolic Diseases (I2MC) at the University of Toulouse wanted to understand why the loss of HSL caused fat tissue to break down instead of build up. What they found changed the scientific picture of fat metabolism.

Scientists Discover HSL Inside the Cell Nucleus

The research team, led by Dominique Langin, discovered that HSL was located in an unexpected place inside adipocytes: the nucleus.

The nucleus acts as the cell’s control center. It contains DNA and regulates which genes are switched on or off. Proteins found in the nucleus often help control cell growth, repair, metabolism, and communication.

“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’,” explained Jérémy Dufau, co-author of the study.

Researchers found that nuclear HSL appears to help regulate important cellular systems, including mitochondrial activity and the extracellular matrix, which provides structural support for tissues.

Mitochondria are often called the power plants of cells because they generate energy. The extracellular matrix helps maintain the shape and integrity of tissues. Problems in either system have been linked to obesity, inflammation, and metabolic disease.

A Protein With Two Very Different Jobs

The study showed that HSL behaves differently depending on where it is located inside the cell.

On lipid droplets, HSL acts as an enzyme that helps release stored fat during fasting or exercise. In the nucleus, however, it appears to work more like a regulator that helps maintain healthy adipose tissue.

Researchers also discovered that the amount of HSL inside the nucleus changes in response to the body’s metabolic state.

During fasting, adrenaline activates HSL and pushes it out of the nucleus so it can help mobilize fat stores. In obese mice fed a high-fat diet, nuclear HSL levels increased.

The protein’s movement appears to be controlled by signaling pathways involving TGF-β and SMAD3, molecules already known to influence inflammation, tissue remodeling, and metabolic disease.

Scientists also found evidence that nuclear HSL interacts with proteins involved in gene expression and RNA processing, suggesting it may directly influence how fat cells function at a genetic level.

Why the Discovery Matters

The findings helped explain why complete HSL deficiency causes lipodystrophy instead of obesity. Without HSL in the nucleus, fat cells may lose their ability to stay healthy and properly maintain adipose tissue.

“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,” Langin said.

The discovery may also help researchers better understand why some obesity treatments succeed while others fail. Many current therapies focus mainly on reducing fat mass. But the study suggests preserving healthy fat tissue function could be equally important.

Scientists are increasingly recognizing that adipose tissue acts as a complex endocrine organ that communicates with the brain, liver, muscles, and immune system through hormones and signaling molecules. Dysfunctional fat tissue can disrupt the body far beyond weight gain alone.

Obesity Remains a Global Health Challenge

The research arrives as obesity rates continue to rise worldwide. According to global estimates, billions of people are now overweight or obese, increasing the risk of diabetes, heart disease, stroke, sleep apnea, and some cancers.

Researchers hope that understanding how proteins like HSL regulate fat cell health could eventually lead to more targeted therapies for metabolic disease.

Instead of simply trying to eliminate fat, future treatments may focus on restoring the normal function of adipocytes and protecting the biological systems that keep fat tissue healthy in the first place.

Researchers at Tohoku University Graduate School of Medicine uncovered an unexpected possibility involving a drug that has long been used to treat constipation. In a clinical trial, the medication lubiprostone appeared to slow the decline of kidney function in patients with moderate CKD, raising hopes for an entirely new approach to kidney disease treatment.

“We noticed that constipation is a symptom that often accompanies CKD, and decided to investigate this link further,” explains Abe. “Essentially, constipation disrupts the intestinal microbiota, which worsens kidney function. Working backwards, we hypothesized that we could improve kidney function by treating constipation.”

The Surprising Gut Kidney Connection

Doctors have increasingly focused on what researchers call the “gut kidney axis,” the complex relationship between intestinal bacteria and kidney health. People with CKD often experience constipation and imbalances in gut microbes, which can contribute to inflammation and the buildup of harmful compounds in the body.

Earlier research had hinted that improving gut health might help protect the kidneys, but evidence in humans remained limited. To explore the idea further, researchers launched the multicenter Phase II clinical trial known as the LUBI-CKD TRIAL across nine medical institutions in Japan.

The study enrolled 150 patients with moderate chronic kidney disease. Participants received either lubiprostone or a placebo, allowing scientists to compare how the treatment affected kidney function over time.

The results surprised the researchers. Patients who received either 8 µg or 16 µg doses of lubiprostone showed a slower decline in kidney function compared with those in the placebo group. Kidney performance was measured using estimated glomerular filtration rate (eGFR), one of the most widely used indicators of kidney health.

Researchers reported that the protective effect appeared dose dependent, meaning higher doses were linked to greater benefits. The 16 µg group showed particularly promising preservation of kidney function signals during the 24 week trial period.

How a Constipation Drug May Protect the Kidneys

Scientists then investigated why the drug appeared to help the kidneys.

Their analysis pointed to changes in the gut microbiome. Lubiprostone increased the production of spermidine, a naturally occurring compound tied to healthier mitochondrial activity. Mitochondria are often described as the power plants of cells because they generate the energy cells need to function properly.

The researchers found that improved mitochondrial function may help shield kidney tissue from further damage. They also identified changes in bacterial pathways connected to polyamine production, adding more evidence that gut microbes may directly influence kidney health.

Interestingly, the treatment did not significantly reduce certain uremic toxins that scientists originally expected to change. Instead, the kidney benefits seemed tied more closely to microbiome remodeling and mitochondrial support. That finding could reshape how researchers think about treating CKD in the future.

Why Researchers Are Excited About the Findings

The study has drawn attention because lubiprostone is already an approved medication for chronic constipation, potentially making future clinical use faster than developing a completely new drug from scratch.

Researchers also believe the discovery may have implications beyond kidney disease. Because mitochondrial dysfunction is involved in many chronic illnesses, scientists are exploring whether similar gut targeted approaches could eventually help other disorders as well.

The research team is now planning larger Phase 3 trials to confirm whether the benefits hold up in broader patient populations. Scientists are also searching for biomarkers that could predict which patients are most likely to respond to treatment.

Although more research is still needed, the findings have added momentum to a rapidly growing area of medicine focused on the connection between gut bacteria, cellular energy production, and chronic disease progression. For people living with CKD, even modest slowing of kidney decline could potentially delay dialysis and improve quality of life.

Inside the human mouth, bacteria are in near constant communication. Roughly 700 bacterial species live there, and many exchange chemical messages through a process called quorum sensing. Some of these microbes communicate using signaling molecules known as N-acyl homoserine lactones (AHLs).

Researchers from the College of Biological Sciences and the School of Dentistry set out to investigate how these bacterial signals shape the oral microbiome and whether interrupting those signals could help prevent harmful plaque buildup while preserving healthy bacteria. Their findings, published in npj Biofilms and Microbiomes, could eventually influence treatments far beyond dentistry.

Scientists Target Bacterial Communication

The research team discovered several important patterns in how mouth bacteria interact:

• Bacteria living in dental plaque produce AHL signals in aerobic environments (such as above the gumline), and those signals can still affect bacteria in anaerobic environments (beneath the gumline).
• Removing AHL signals using specialized enzymes called lactonases increased populations of bacteria associated with good oral health.
• The findings suggest that carefully selected enzymes may be able to reshape dental plaque communities and support a healthier oral microbiome.

“Dental plaque develops in a sequence, much like a forest ecosystem,” said Mikael Elias, associate professor in the College of Biological Sciences and senior author of the study. “Pioneer species like Streptococcus and Actinomyces are the initial settlers in simple communities — they’re generally harmless and associated with good oral health. Increasingly diverse late colonizers include the ‘red complex’ bacteria like Porphyromonas gingivalis, which are strongly linked to periodontal disease. By disrupting the chemical signals bacteria use to communicate, one could manipulate the plaque community to remain or return to its health-associated stage.”

Oxygen Levels Change Bacterial Behavior

The researchers also found that oxygen plays a surprisingly important role in determining how these bacterial messages influence plaque growth.

“What’s particularly striking is how oxygen availability changes everything,” said lead author Rakesh Sikdar. “When we blocked AHL signaling in aerobic conditions, we saw more health-associated bacteria. But when we added AHLs under anaerobic conditions, we promoted the growth of disease-associated late colonizers. Quorum sensing may play very different roles above and below the gumline, which has major implications for how we approach treatment of periodontal diseases.”

This discovery suggests that bacterial communication works differently depending on where bacteria live inside the mouth. That insight could help researchers design more targeted approaches to controlling gum disease and maintaining a healthier balance of microbes.

Future Treatments Could Protect Healthy Bacteria

The next phase of the research will examine how bacterial signaling differs across various areas of the mouth and in people with different stages of periodontal disease.

“Understanding how bacterial communities communicate and organize themselves may ultimately give us new tools to prevent periodontal disease — not by waging war on all oral bacteria, but by strategically maintaining a healthy microbial balance,” said Elias.

Researchers believe this strategy could eventually be expanded beyond oral health. Imbalances in the microbiome, known as dysbiosis, have been linked to numerous diseases throughout the body, including certain cancers. Scientists hope these findings could help lay the groundwork for future therapies that guide microbial communities toward healthier states rather than eliminating bacteria altogether.

Funding for the study was provided by the National Institutes of Health.