Recently, researchers from the University of Cambridge published a research paper titled "Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting" in Cell Reports. The study uncovers how fasting helps prevent inflammation. Fasting can increase the level of arachidonic acid in the blood, and arachidonic acid can reduce the activity of the NLRP3 inflammasome, thereby inhibiting inflammation. The findings also help explain some of the beneficial health effects of drugs like aspirin.
"We are very interested in trying to understand the causes of chronic inflammation in many human diseases, especially the role of the inflammasome." The corresponding author of the paper, Professor Clare Bryant from the Department of Medicine at the University of Cambridge, said, "In recent years, we have discovered that a specific inflammasome, the NLRP3 inflammasome, plays an important role in many major diseases, including metabolic diseases such as obesity and atherosclerosis, neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, and many age-related diseases, especially in the Western world."
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Fasting can help reduce inflammation, but why is unclear. To help answer this question, a team of researchers from the University of Cambridge and the National Institutes of Health recruited 21 volunteers. The volunteers ate a 500-calorie meal, then fasted for 24 hours, then had a second 500-calorie meal, and their blood samples were studied and analyzed.
The research team found that fasting increases levels of a lipid called arachidonic acid, and when eating again, levels of arachidonic acid decrease. Lipids are molecules that play important roles in the body, such as storing energy and carrying information between cells.
The research team further explored the role of arachidonic acid in laboratory-cultured immune cells and found that arachidonic acid reduced the activity of the NLRP3 inflammasome. This finding came as a surprise to them because arachidonic acid had previously been linked to increased levels of inflammation, rather than lowering them.
Figure 1. AA inhibits NLRP3-mediated IL-1β production by blocking the activities of phospholipase C and the downstream protein kinases PKD and JNK. (Pereira M, et al., 2024)
Specifically, the study found that in fasted subjects whose serum IL-1β was suppressed, arachidonic acid levels were elevated and reversed upon refeeding. NLRP3 stimulation induces macrophages to produce lipids, including arachidonic acid and eicosatrienoic acid. But only arachidonic acid significantly inhibited the NLRP3 inflammasome by inhibiting phospholipase C (PLC) and JNK activity. Treatment of macrophages with nonsteroidal anti-inflammatory drugs (NSAIDs, such as aspirin) inhibited NLRP3 activity and prostaglandin production, but arachidonic acid levels remained unchanged.
These data demonstrate that arachidonic acid is an important physiological regulator of the NLRP3 inflammasome and provide a mechanism to explain why fasting reduces systemic inflammation. It also helps reveal some of the beneficial health effects of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin.
Reference
Pereira M, et al. Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting. Cell Reports, 2024, 43(2).