AI-Powered Whole-Body Mapping Reveals Obesity’s Hidden Impact on Facial Nerves

Key Takeaways: 

• Researchers have developed an AI-driven whole-body imaging platform called MouseMapper that can analyse disease-related changes across an entire mouse body at cellular-level resolution.
  
• Using the system, scientists identified widespread inflammation and previously unknown damage to facial sensory nerves linked to obesity.
  
• Similar molecular patterns were also detected in human tissue, suggesting that obesity-related nerve changes observed in mice may also occur in people.
  
  
  

A new way to study disease across the entire body

Researchers from Helmholtz Munich, Ludwig Maximilians University Munich (LMU), and several collaborating institutions have developed a powerful artificial intelligence-based imaging system capable of mapping disease-related changes throughout an entire mouse body in extraordinary detail.

The new platform, known as MouseMapper, combines advanced whole-body imaging with foundation-model-based AI to examine how diseases affect organs, nerves, immune cells, and tissues simultaneously. Using the system, the research team uncovered widespread inflammation and previously unrecognised nerve damage associated with obesity.

The findings, published in Nature, also revealed similar molecular signatures in human tissue, suggesting that some obesity-related nerve damage mechanisms may occur in both mice and people.

Obesity is increasingly recognised as a complex disease that affects far more than body weight and metabolism. It can alter immune activity, disrupt nerve structures, and reshape tissues across the body, contributing to conditions including type 2 diabetes, cardiovascular disease, stroke, neuropathy, and cancer. However, despite these systemic effects, researchers have lacked technologies capable of studying disease-related changes throughout an intact body at high resolution.

To address this limitation, the research team led by Professor Ali Ertürk, Director of the Institute for Biological Intelligence (iBIO) at Helmholtz Munich and Professor at LMU, created MouseMapper.

The AI framework uses deep learning algorithms based on foundation models to analyse enormous whole-body imaging datasets. The system can automatically identify and segment 31 different organs and tissue types while simultaneously mapping nerves and immune cells throughout the body.

This enables scientists to investigate how diseases affect multiple organ systems at the same time rather than analysing tissues individually.

“MouseMapper is built on a foundation model, which means it generalizes far beyond the data it was originally trained on,” says Ying Chen, co-first author of the study.

Transparent mice enable deep whole-body imaging

To generate the body-wide maps, the researchers first labelled nerves and immune cells in mice using fluorescent markers that glow under microscopic imaging.

The team then used specialised tissue-clearing techniques to render the mice transparent while preserving the fluorescent signals. This allowed scientists to visualise structures deep inside the body without physically cutting tissues into sections.

Researchers next employed advanced light-sheet microscopy to produce highly detailed three-dimensional images of entire mice. These scans generated extremely large datasets containing tens of millions of cellular structures distributed across multiple organs and tissues.

MouseMapper then processed the data automatically, identifying anatomical structures, nerve networks, and clusters of immune cells throughout the animals.

Unlike conventional approaches that require scientists to select specific tissues or regions for analysis beforehand, the system enabled the researchers to examine disease-related changes across the whole organism simultaneously.

This whole-body approach allowed the team to pinpoint where inflammation and tissue damage were occurring in organs including fat tissue, muscle, liver, and peripheral nerves.

Obesity found to alter facial sensory nerves

To investigate how obesity affects the body, the researchers fed mice a high-fat diet that induced obesity and metabolic disturbances similar to those observed in humans.

Using MouseMapper, the scientists identified widespread changes in both immune-cell organisation and nerve structures throughout the body.

One of the most unexpected findings involved the trigeminal nerve, a major facial nerve responsible for transmitting facial sensations and supporting certain motor functions.

The researchers discovered that obese mice showed a substantial reduction in nerve branches and sensory nerve endings within these facial nerves, suggesting impaired nerve function.

Behavioural testing supported this observation. Obese mice demonstrated reduced responsiveness to sensory stimulation compared with lean mice, indicating that the structural changes may have functional consequences.

Molecular changes detected in facial nerve tissue

The team then carried out a more detailed investigation of the trigeminal ganglion, the structure that contains the cell bodies of facial sensory neurons.

Using spatial proteomics analysis, the researchers identified molecular alterations associated with inflammation and nerve remodelling within the trigeminal ganglion.

Importantly, many of the same molecular signatures identified in mice were also found in trigeminal tissue samples from people living with obesity.

This suggests that the nerve-related changes observed in the animal models may also occur in humans.

“We revealed previously unknown structural and molecular changes in the trigeminal ganglion and its facial branches, and the same molecular signature was conserved in human tissue. This kind of finding simply cannot emerge from studying one organ at a time,” says Dr. Doris Kaltenecker, senior scientist at the Institute for Diabetes and Cancer (IDC) at Helmholtz Munich and first author of the study.

Potential applications beyond obesity

The researchers believe MouseMapper could become an important platform for studying diseases that affect multiple organ systems simultaneously.

Potential future applications include research into diabetes, cancer, neurodegenerative diseases, and autoimmune disorders.

Unlike traditional methods that focus on isolated tissues or organs, MouseMapper provides an integrated whole-body analysis system capable of identifying disease “hotspots” throughout an organism.

The research team has also made the whole-body datasets publicly available online, allowing scientists worldwide to explore obesity-related changes across tissues and organs.

“Our goal is to create a comprehensive framework for understanding how diseases affect the body as an interconnected system,” says Ali Ertürk.

“Our long-term vision is to build truly realistic digital twins of mice in health and disease: cell-level atlases that we can query, perturb and screen in silico computationally. That would let us pinpoint the earliest changes a disease causes, design interventions to prevent them, and accelerate the discovery of new treatments while reducing the number of physical experiments we need to run.”

Research funding and support

The study received support from multiple funding organisations and research initiatives, including the European Research Council, the German Research Foundation under Germany’s Excellence Strategy, the Munich Cluster for Systems Neurology (SyNergy), the German Federal Ministry of Education and Research, the Vascular Dementia Research Foundation, the Nomis Foundation, the Else-Kröner-Fresenius-Stiftung, the Edith-Haberland-Wagner Stiftung, the Helmut Horten Foundation, the EFSD and Novo Nordisk A/S Programme for Diabetes Research in Europe, and the China Scholarship Council.