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Crush Inflammation with Fasting- Here’s How!

During inflammation, our cells switch toward the ATP production via glycolysis even in the presence of oxygen – a process called aerobic glycolysis. Therefore, in an inflammatory state, we have more immune cells and these cells use glucose at a very rapid rate. This makes glucose less available for other tissues and makes us feel fatigued.

In certain tissues, the switch towards glycolysis might lead to an even more serious problem like cancer. Aerobic glycolysis is called the Warburg effect and it was discovered in cancer cells. Tumours show exceptional rates of aerobic glycolysis. For doing so, they need to upregulate the enzymes required for aerobic glycolysis. The production of these enzymes can be stimulated by cytokines. The action of these cytokines facilitates the metabolic switch of immune cells.

A study published in Cancer Biology and Therapy reported that an environment of chronic inflammation in the gut can promote the progression from colitis to cancer. They found out that once the cells of gut barrier get exposed to IL-6, same as immune cells, they also start to exhibit higher production of glycolytic enzymes. This means that the cells in the inflammatory environment get reprogrammed closer to the metabolic stage of a cancer cell. It must be noted here that chronic inflammation is estimated to contribute to 25% of all human cancer cases.

In hypothesis, this research also implies that the chronic inflammatory environment can reprogram our cells to rely on a less effective mean of obtaining energy, leading to fatigue again.

Further, inflammation is connected with higher mitochondrial reactive oxygen species (ROS) production. Increased ROS permeabilize mitochondria as it creates holes in their membranes. As the mitochondrial membrane is the site of the effective oxidative phosphorylation, any damage can further decrease its ability to produce ATP.

Mechanism of Fasting Supressing Mechanism

Here we proposed few mechanisms of how chronic inflammation can strip us away from energy. The increased number of immune cells utilize a lot of glucose through not very efficient glycolysis. In the gut, it can even reprogram other cells to rely more on the ineffective glycolysis. Lastly, it can damage our mitochondria, the site of energy production.

A study published in Cell reported that 19-hour fast drastically reduces the number of circulatory monocytes. Researchers also examined the molecular mechanism of the decrease. During a metabolic switch, as seen previously with a switch from oxidative phosphorylation to glycolysis, we need upregulation of enzymes that will facilitate such a switch. During fast we switch from carbohydrate to fats with the help of transcription factor called PPAR which is activated by fasting.

In this study, they found that PPAR acts on immune cells as well. PPAR suppresses CCL2, a recruiter of monocytes from the bone marrow, the primary site of monocytes production. Further, during fasting a decreased level of energy are present. This is sensed by an AMPK pathway, which acts as an energy sensor. This pathway was shown to regulate the egress of monocytes from the bone marrow.

References

https://pubmed.ncbi.nlm.nih.gov/24115022/
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https://www.thelancet.com/article/S2352-3964(18)30355-4/pdf
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https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-019-1411-x