Researchers have identified key cellular markers in obese individuals that could predict metabolic health, offering new avenues for treatment and prevention of diabetes, high blood pressure and cholesterol.
Researchers led by ETH Zurich and the University of Leipzig have unveiled new insights into why some obese individuals develop severe health conditions like diabetes, high blood pressure and high cholesterol, while others remain metabolically healthy.
Their comprehensive study, published in the journal Cell Metabolism, sheds light on the genetic activity within fat tissue, offering hope for new diagnosis and treatment methods.
Decoding the Health Puzzle of Obesity
Although obesity is often linked with a range of metabolic diseases, around 25% of obese individuals manage to avoid these conditions. Intrigued by this phenomenon, the researchers aimed to understand the underlying factors differentiating healthy and unhealthy obese people.
“Our results can be used to look for cellular markers that provide information on the risk of developing metabolic diseases,” co-lead author Adhideb Ghosh, a lecturer in the Department of Health Sciences and Technology at ETH Zurich and a member of the Laboratory of Translational Nutrition Biology headed by Christian Wolfrum, said in a news release. “The data is also of great interest for basic research. It could help us develop new therapies for metabolic diseases.”
A Wealth of Data From the Leipzig Obesity Biobank
The research team utilized the Leipzig Obesity Biobank, comprising biopsies from obese patients who consented to donate adipose tissue during elective surgeries. This extensive collection allowed scientists to compare fat tissue from individuals with and without metabolic diseases, focusing on gene activity in subcutaneous and visceral fat.
“Visceral fat, which lies deep in the abdominal cavity and surrounds the internal organs, is primarily responsible for metabolic diseases,” added second lead author Isabel Reinisch, a postdoc in Wolfrum’s group. “In fact, the adipocytes are in the minority.”
Adipose tissue consists of various cells, including immune cells, blood vessel-forming cells and immature precursor cells of adipocytes.
Significant Cellular Differences in Metabolically Healthy vs. Unhealthy Individuals
The study revealed considerable functional changes in the cells of visceral adipose tissue among those with metabolic diseases. These alterations affected nearly every cell type within the tissue.
For example, the adipocytes of unhealthy individuals struggled to burn fats efficiently and produced higher quantities of immunologic messenger molecules.
“These substances trigger an immune response in the visceral fat of obese people,” added Reinisch. “It’s conceivable that this response promotes the development of metabolic diseases.”
In contrast, healthy obese individuals showed a higher proportion and greater functional flexibility of mesothelial cells in visceral fat. These cells could switch to a sort of stem cell mode to convert into various cell types, aiding smooth tissue expansion, a capability typically associated with cancer cells.
Moreover, the research found gender-specific differences, with a particular type of progenitor cell present only in the visceral fat of women.
“This could explain differences in the development of metabolic diseases between men and women,” Reinisch added.
Future Implications and Research Directions
The newly developed atlas of gene activity in obese individuals elucidates the composition and function of various cell types within adipose tissue. However, the study does not conclusively determine whether these cellular differences cause metabolic health or result from it.
“[W]e cannot say whether the differences are the reason why someone is metabolically healthy or whether, conversely, metabolic diseases cause these differences,” added Ghosh.
Nonetheless, this atlas offers a crucial foundation for future research.
Publishing their data in a publicly accessible web app, the researchers aim to facilitate further investigations and identify biomarkers indicating the risk of metabolic diseases. Such markers could significantly enhance treatment strategies, particularly concerning new drugs that suppress appetite and promote insulin release, which are in short supply.
“Biomarkers that can be derived from our data could help to identify those patients who are most in need of this treatment,” Reinisch concluded.