A pioneering study conducted by researchers from Zurich and Leipzig has uncovered new insights into the complexities of fat tissue and its role in metabolic health. The research challenges the traditional understanding of obesity, revealing that not all individuals with excess weight experience the same health issues. While obesity is widely recognized as a risk factor for various diseases, some overweight individuals remain metabolically healthy, sparking questions about the factors that contribute to this disparity.
The study, which focused on fat tissue, particularly visceral fat (the fat stored deep in the abdomen), provides critical information about the ways fat cells function and how their dysfunction can contribute to health problems. Visceral fat has long been linked to a heightened risk of metabolic diseases, as its accumulation can disrupt metabolic processes and trigger inflammation.
Recent advancements in single-cell and single-nucleus transcriptomics have made it possible for scientists to gain a deeper understanding of how fat tissue changes in response to obesity. However, key questions about the connection between fat cells, gene expression, and disease progression remain.
To address these questions, the researchers utilized data from the Leipzig Obesity Biobank, which contains tissue samples from obese individuals who underwent elective surgeries and consented to donate their fat tissue for research. By examining fat tissue from 70 volunteers—both healthy and unhealthy overweight individuals—the researchers mapped cellular changes in fat tissue and linked them to metabolic health.
The team focused on two types of fat: subcutaneous fat, located just beneath the skin, and visceral fat. Using advanced techniques such as snRNA sequencing and bulk RNA sequencing deconvolution, they identified obesity-related cellular alterations and uncovered specific cell types associated with metabolic issues.
Their findings revealed significant changes in the composition of visceral fat cells in individuals with metabolic diseases. In particular, fat cells in unhealthy individuals were less efficient at burning fats and produced elevated levels of immune-related molecules. These molecules, according to Isabel Reinisch, a postdoctoral researcher in the study, may trigger immune responses in the visceral fat, which could potentially contribute to the development of metabolic diseases.
Interestingly, the researchers also identified notable differences in mesothelial cells between healthy and unhealthy obese individuals. Healthy individuals exhibited more flexible mesothelial cells, which could adapt to a stem cell-like state, enabling them to become various cell types that support tissue expansion.
Gender-specific differences were another key aspect of the study. The researchers discovered a unique progenitor cell found only in the visceral fat of women. This finding could offer insight into the differing ways men and women develop metabolic diseases.
While the new atlas sheds light on the diversity of cells in fat tissue and their functions, it does not conclusively determine whether these cellular changes are the cause or the result of metabolic health problems. The research team has made their findings available through an online platform, encouraging further investigation into these complex interactions.
This new resource is expected to open doors for discovering novel markers associated with metabolic diseases, offering potential pathways for improved diagnostics and treatments. Researchers at ETH Zurich are also exploring how this data can be used to identify patients who may benefit most from emerging treatments, such as appetite-suppressing drugs and therapies aimed at promoting insulin release.
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