Obesity is increasing worldwide and is linked to health problems, but not everyone with obesity develops these issues. Some people with obesity are still considered metabolically healthy.
The fat inside the abdomen (visceral fat) is a key predictor of health risks because dysfunction in fat tissue affects metabolism and increases the risk of diseases.
Recent advances in single-cell and single-nucleus transcriptomics have provided new insights into the complexity of fat tissue and how it responds to obesity. However, there is still limited understanding of how different cell populations and their gene expression relate to disease severity.
Researchers from Zurich and Leipzig created a detailed map of cellular changes in obese people using data from both healthy and unhealthy overweight individuals. They focused on fat tissue and gene activity, considering factors like fat location, amount, and gender.
They used the Leipzig Obesity Biobank, which contains tissue samples from obese individuals who had elective surgery and consented to donate their fat tissue for research. These samples allowed comparison between healthy and unhealthy obesity.
They examined the gene activity in fat tissue samples from 70 volunteers, focusing on two types of fat: subcutaneous (under the skin) and visceral (deep in the abdomen).
Using snRNA sequencing, deconvolution of bulk RNA-sequencing datasets, and unsupervised MOFA cells, the researchers created a map showing obesity-related cellular changes and identified cell types strongly linked to metabolic health problems.
They found significant changes in visceral fat cells in people with metabolic diseases, affecting almost every cell type. For example, unhealthy individuals’ fat cells couldn’t burn fats effectively and produced more immune-related molecules.
Isabel Reinisch, a postdoc in Wolfrum’s group and the study’s second, said, “These substances trigger an immune response in the visceral fat of obese people. It’s conceivable that this response promotes the development of metabolic diseases.”
They found significant changes in visceral fat cells in people with metabolic diseases, affecting almost every cell type. For example, unhealthy individuals’ fat cells couldn’t burn fats effectively and produced more immune-related molecules.
They also found differences in mesothelial cells, with healthy obese individuals having more flexible cells that can switch to a stem cell-like mode and become different types of cells, helping in tissue expansion.
Additionally, they discovered gender differences, with a specific type of progenitor cell present only in the visceral fat of women, possibly explaining differences in disease development between men and women.
The new atlas shows the types of cells in fat tissue and their functions but doesn’t clarify if the differences cause metabolic health issues or vice versa. The researchers made the data available in a web app for further studies.
This atlas can help find new markers for developing metabolic diseases. ETH researchers are also looking for such markers to improve treatments, such as identifying patients most in need of new drugs that suppress appetite and promote insulin release.
Journal Reference:
- Isabel Reinisch, Adhideb Ghosh et al. Unveiling adipose populations linked to metabolic health in obesity. Cell Metabolism 2025, 37: 1, DOI: 10.1016/j.cmet.2024.11.006
Pranjal Malewar
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