Alternate Fuel ‘Cells’ Redefines Function of Nutrition in the Immune System

A metabolic by-product that is more prominent during fasting can improve immune cells’ ability to fight off infection and disease, according to a preliminary study conducted by researchers at the Van Andel Institute and its partners.

Alternate Fuel ‘Cells’ Redefines Function of Nutrition in the Immune System
Dr. Russell Jones, Van Andel Institute. Image Credit: Van Andel Institute

The research, which was published on July 28th, 2023 in the journal Immunity, could pave the way for future customized dietary advice to promote treatment options for cancer, infections, and other diseases.

This study helps us better understand how nutrition affects the immune system. This is an exciting first step and we look forward to one day translating this knowledge into dietary recommendations to boost immune function.

Russell Jones, PhD, Study Corresponding Author and Professor, Van Andel Institute

The findings are centered on ketone bodies, which are normally created by the liver but increase in quantity when there is a shortage of glucose, a sugar that serves as the primary energy source for cells.

During periods of fasting, when there is little food available to be broken down into glucose, or during periods of effort like exercise when cells are quickly burning through fuel, this can happen.

Image Credit: Image Credit: Design_Cells/Shutterstock.com

Image Credit: Image Credit: Design_Cells/Shutterstock.com

To compensate, the liver increases ketone body synthesis to nourish the brain and other organs. The study found that ketone bodies also energize immune cells, which is a surprising discovery that sheds light on new links between nutrition and immunity.

T cells, the immune system’s warriors, take up nutrients like glucose from meals to provide them the energy they need to carry out their duties, much like other body cells do. Jones and colleagues showed that the preferred fuel for T cells is ketone bodies rather than glucose.

Additionally, they discovered that ketone bodies enhance T cell performance by reprogramming them to more effectively destroy threats. On the other hand, T cells’ ability to fight infection is compromised when their capacity to metabolize ketone bodies is lost.

This work underscores how different nutrient fuels source distinct cellular functions. It also fosters future interest in considering the diversity of nutrient fuel utilization patterns among different immune cell types in varying infectious disease or cancer contexts.

Peter Crawford, MD, PhD, Study Co-Author and Professor, Medicine, University of Minnesota

The study implies that elevating ketone bodies by fasting or intermittent fasting regimens could boost T cell activity in some situations, while other studies suggest that fasting could reduce immune function.

These studies show how closely the immune system and diet interact, rather than showing how they are in conflict with one another and highlighting the need for more investigation into this nuanced relationship.

Jones and colleagues will continue to investigate the effects of fasting and ketone body supplementation on immune function, with particular emphasis on T cells’ capacity to combat cancer.

Source:
Journal reference:

Luda, K. M., et al. (2023). Ketolysis drives CD8+ T cell effector function through effects on histone acetylation. Immunity. doi.org/10.1016/j.immuni.2023.07.002

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