The omega-3 fatty acids, which we mainly get through the consumption of fatty fish, have long been considered good for our health. Many dietary studies have suggested that high intake is associated with a reduced risk of various disorders. Clinical studies have also shown beneficial anti-inflammatory effects in patients taking omega-3 supplements. Recent research by NTNU supports previous discoveries and has also found new, useful effects of omega-3 supplements and how these lipids dampen harmful inflammatory reactions in the body. Despite numerous published dietary and clinical studies, we do not yet understand how omega-3 fatty acids act on our cells and whether this varies from person to person, between healthy and diseased individuals or if the mechanism of action varies in different tissues and cells. What we are more sure about is that omega-3 fatty acids can dampen inflammatory reactions. Inflammatory reactions are very important in the fight against infections, but they can be harmful if activated too strongly or in the absence of bacteria and viruses, as in autoimmune diseases and organ transplants. Macrophages, which are immune cells that live in all tissues and organs, play a key role in coordinating inflammatory reactions in the body and monitoring everything that happens in our tissues. Macrophages convert the information they get through various sensors or receptors on their surface to the secretion of various signal substances similar to hormones (cytokines) that control all parts of the inflammatory reactions.
We are increasingly aware that macrophages can be more or less powerful in activating inflammatory reactions. So-called sterile inflammatory reactions, such as autoimmune diseases, are often directly harmful. The ability of macrophages to stimulate inflammatory reactions depends on the processes within macrophages. Autophagy is one of the processes within macrophages that is important if a macrophage is calm or hyperactive. Autophagy (which means “self-eating”) is a key process for the degradation of non-functional or unnecessary proteins and other components within our cells. In recent years, we have learned a lot about how important this process is, say the researchers. The Nobel Prize in Physiology or Medicine 2016 was awarded to Yoshinori Ohsumi for the discovery of key genes that control autophagy. Autophagy constantly continues in all cells and increases if the cells are hungry or injured. It has been hypothesized that omega-3 fatty acids could dampen inflammatory reactions by increasing autophagy in macrophages. If so, this effect could change the transformation of the signal in the macrophage and, consequently, suppress the activation of inflammatory reactions. By studying macrophages isolated from mice and humans, scientists have discovered that omega-3 fatty acids activate autophagy and in particular influence certain proteins that transform signals from the environment.
Moreover, they have shown that omega-3 fatty acids have attenuated many inflammatory mechanisms within macrophages, but especially reduced what is known as a response to type 1 interferon. CXCL-10 is a type of cytokine defined as chemokine, which macrophages secrete as part of this interferon response following many types of stimuli, and was the most clearly reduced factor after adding omega-3 to cells. The team then examined blood samples from a clinical study of patients undergoing heart transplantation, in which they knew that omega 3 supplements improved their clinical status. In these cases, it was found that omega-3 fatty acids reduced the level of CXCL-10. Autophagy thus changes in macrophages in response to omega-3 fatty acids and specifically inhibits the secretion of inflammatory factors belonging to the interferon response, with CXCL-10 showing the clearest reduction. Previously, the team reported that physiologically relevant doses of the omega-3 called DHA increased the turnover of “labeled” proteins in retinal pigment cells (ARPE-19), probably reducing the risk of age-related macular degeneration. The plasma level of CXCL10 is reduced by omega-3 intake but increased in the placebo group in hypertensive heart transplant patients.
These results indicate that omega-3 fatty acid supplements may be particularly useful in patients who have conditions that are guided or exacerbated by a strong response to the interferon and CXCL-10. These could include patients with different forms of cancer, meningitis, multiple sclerosis and Alzheimer’s disease.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Mildenberger J et al. Autophagy. 2017 Oct 3; 13(10):1664-1678.
Sheridan DA, Bridge SH et al. Liver Int. 2014 May; 34(5):737-47.
Lu Y, Zhao LX, Cao DL, Gao YJ. Neuroscience. 2013; 241:22-31.