Slowing down how quickly the body makes a specific type of fat could help to combat type 2 diabetes, according to new research published online in the journal eLife.
A team of researchers, led by Dr Kasparas Petkevicius, Dr Samuel Virtue and Professor Toni Vidal-Puig of the Wellcome-MRC Institute of Metabolic Science, has made the discovery whilst studying macrophages, which are immune system cells.
Macrophages can become activated during a process known as inflammation. While inflammation can help fight bacteria and heal injuries, obesity can trigger macrophages in fat tissue to become inappropriately activated and increase insulin resistance, which is an important factor in type 2 diabetes.
The researchers were studying how changes in fat metabolism might cause macrophages to become inappropriately activated in obesity. To do so, they partially deleted a gene called Pcyt1a in particular cells, including macrophages, in mice.
Pcyt1a makes a type of fat called phosphatidylcholine (PC). When they deleted Pcyt1a, they expected to see lower PC levels in the macrophages – but surprisingly, the levels of PC stayed the same. When they reduced the amount of PC being made, the macrophages responded by reducing the amount of PC they eliminated. Importantly, this made the macrophages resistant to the effects of other toxic fats. Having slower turnover of PC in the macrophages was found to be better for the cell, because the longer the PC remains in macrophages, the more unsaturated fatty acid it contains.
The researchers went on to show that in a mouse that was very obese, reducing the amount of new PC produced in its macrophages made it healthier. Importantly, macrophages from the fat tissue of obese people have increased markers of PC production, suggesting that it may cause their fat tissue to be unhealthy.
Dr Kasparas Petkevicius said:
These findings are exciting. While complete loss of the gene we studied is lethal, our results suggest fine-tuning how quickly fat is made by the body might allow us to treat people with obesity without harmful side-effects.
Professor Toni Vidal-Puig, senior author said:
With obesity levels on the rise, it is increasingly important to understand how obesity leads to metabolic diseases like diabetes.
Dr Maeve Elder, Research Advisor at the British Heart Foundation, added:
With more than 3.8 million adults diagnosed with diabetes in the UK, and the condition increasing the risk of heart and circulatory diseases, it is crucial we fund new research to help combat it.
Although more research will be needed to ensure these findings are applicable to humans, this study suggests that slowing down fat production could combat harmful inflammation in obesity which can increase insulin resistance and potentially trigger type 2 diabetes.
This research has only been made possible by the fantastic generosity of the public and their support to drive forward our mission to beat heartbreak forever.
The study was funded by the British Heart Foundation (BHF), Medical Research Council (MRC) and Wellcome.
Image credit: NIAID (CC0). Microscopy image of a macrophage.