LipoLUNG: Adipose Triglyceride Lipase in lung cancer

For many decades cancer research was mainly focused on the fight against fast growing cancer cells. About a century ago it however, became clear that the metabolism of cancer cells is probably quite different to the metabolism of most normal cells in our body. Based on this principle, several new routes to fight cancer are tested and established, nowadays. The research proposed in our grant, focuses on the role of an enzyme that is needed to activate energy from fat depots. Therefore, it is called Adipose TriGlyceride Lipase, or in short, ATGL. Interestingly, we have recently found out that absence of ATGL is linked to lung cancer and that animals where ATGL is absent, get lung cancer. Currently, we think that ATGL is needed for normal function of lung cells. Hence, we hypothesize that without ATGL, the lung cannot properly react to the manifold normal challenges that it has to face at a daily basis. These include dust, smoke, pathogens, airborne chemicals and even normal lung surface regeneration processes. As a result, we believe that loss of the metabolic function of ATGL could lead to persistent low level inflammation, eventually triggering cancer. Therefore, we need to find out first in which cells ATGL is needed for normal function and to prevent the onset of lung cancer. Thereafter, we aim to analyze these cells in detail, to understand why they need ATGL and why cancer arises when ATGL is absent. In a time when the metabolic syndrome is a spreading pandemic, it is an intriguing idea that analysis of metabolic markers could lead to earlier identification of cancer predisposition, onset and/or -spread. Therefore, we consider our proposed project as novel and important for cancer research.

Unraveling the Secrets of Lung Repair: How a Special Enzyme Keeps Our Lungs Healthy In lung health, our recent discovery has shed light on a crucial player - adipose triglyceride lipase (ATGL). This enzyme is essential for repairing and renewing club cells in our lungs. These club cells are like the guardians of our airways, dealing with insults we might breathe in that could cause harm. Keeping them in good shape is crucial for overall lung health. Club cells have essential jobs, like creating a protective layer, detoxifying after exposure to harmful things, and regenerating after an injury. But doing all these tasks takes much energy, and that's where ATGL comes in. It's like the energy manager, making sure everything runs smoothly. The research led by our team showed that when ATGL is missing, things go haywire. Club cells start collecting too much fat, lose some essential parts (mitochondria), and weaken our airways. To test this, we exposed mice to harmful chemicals. The mice without ATGL had a hard time fixing their club cells afterward. But giving them a special booster (a PPAR agonist) helped the club cells recover. So, why does this matter for all of us? Understanding how this enzyme and club cells work can help keep our lungs healthy. Finding ways to support ATGL and the club cells could be a powerful tool to help our lungs recover from challenging situations such as severe microbial infections or chronic lung diseases. On the medical front, this knowledge could revolutionize respiratory therapies, offering innovative solutions for individuals facing environmental risks or respiratory conditions. Economically, promoting lung health translates to a more resilient workforce and reduced healthcare burdens, fostering economic sustainability. This research isn't just about science; it's about finding practical ways to keep our lungs strong, especially in a world with rising air quality and environmental challenges. It's a step toward a healthier future where our cells can do their job well: protecting our breath.