Fat droplets protect stem cells against damage from stress

08 October 2015

The developing central nervous system of Drosophila showing that lipid droplets in glia (red) are in close proximity to neural stem cells (green).

Image: The developing central nervous system of Drosophila showing that lipid droplets in glia (red) are in close proximity to neural stem cells (green).

Francis Crick Institute researchers studying fruit flies have identified a new mechanism that protects stem cells from damage caused by polyunsaturated fatty acids during oxidative stress.

Oxidative stress is a metabolic imbalance that makes cells produce highly reactive molecules called free radicals. When these free radicals reach dangerously high levels in diseases such as stroke or neurodegeneration they can damage or even kill cells.

The research team was led by Dr Alex Gould of the Crick. They used the powerful genetic techniques possible in fruit flies to find out how cells that build the brain, known as neural stem cells, protect themselves from the dark side of polyunsaturated fatty acids (polyunsaturates).

Dr Gould explained: "Omega-3 and omega-6 polyunsaturates are essential in the human diet and are often taken as a dietary supplement. During conditions of oxidative stress, however, they are known to be particularly vulnerable to attack by free radicals. This generates harmful chain reactions that can damage many types of molecules within cells."

For their study, the scientists raised Drosophila fruit flies on a diet high in omega-6 polyunsaturated fatty acids. They then exposed the animals to oxidizing chemicals that mimic the oxidative stress that occurs during several human diseases.

 

Top panel shows how lipid droplets in glia minimize the damaging effects of reactive oxygen species (ROS) upon neural stem cells. Bottom panel illustrates that polyunsaturated fatty acids (PUFA) are more prone to chemical attack by ROS in cell membranes than they are in the protective core of lipid droplets.

Top panel shows how lipid droplets in glia minimize the damaging effects of reactive oxygen species (ROS) upon neural stem cells. Bottom panel illustrates that polyunsaturated fatty acids (PUFA) are more prone to chemical attack by ROS in cell membranes than they are in the protective core of lipid droplets. (Click to view larger image)

 

This caused fat droplets to accumulate in the flies' brains. When the scientists used genetic techniques to block the formation of these droplets, they saw a big increase in the cellular damage caused by oxidised polyunsaturates. Further experiments showed that these fat droplets perform an antioxidant role by hiding vulnerable polyunsaturates in their protective core. This helped to decrease the harmful chain reactions that would otherwise occur inside neural stem cells and damage them.

Dr Andrew Bailey, a researcher in the Crick team, said: "This work in fruit flies reveals a new antioxidant role for lipid droplets and shows how they protect the stem cells of the developing brain from free radical damage. Contrary to the prevailing view, we found that lipid droplets forming during oxidative stress can play a beneficial rather than a harmful role."

Dr Gould added: "Lipid droplets are well known to form inside human cells experiencing oxidative stress in stroke, heart disease, neurodegeneration and cancer. Our research in fruit flies now makes it important to test whether lipid droplets also play an antioxidant role in any of these disease contexts. If this is the case for the lipid droplets that form inside tumours, it may be possible to use drugs that block these droplets as a new class of anti-cancer therapy."

The paper, Antioxidant role for lipid droplets in a stem cell niche of Drosophila, is published in Cell.

  • Research in fruit flies shows that fat droplets form inside cells to protect them from the potentially harmful side effects of omega-3 and omega-6 polyunsaturates. The findings identify a new antioxidant process in cells, which may provide a target for future disease therapies.
  • The research was carried out by Francis Crick Institute scientists with colleagues at Southampton General Hospital and Harvard Medical School.