Link between dietary intake, energy metabolism and immunity

Jordan S, Tung N, Casanova-Acebes M, et al. Dietary intake regulates the circulating inflammatory monocyte pool. Cell 2019;178:1102–14.

This paper starts from a very simple but striking observation, that the number of circulating monocytes in blood varies between fasting and fed states, in human volunteers and in mice. The change in circulating inflammatory monocytes during fasting was due to reduced egress from the bone marrow and was reversible on feeding. Further refinement demonstrated that intake of carbohydrates and protein influenced circulating monocyte numbers but interestingly, feeding mice with fat did not have an effect. Altering cellular energy metabolism through inhibition of glycolysis or 5' AMP-activated protein kinase (AMPK) activation had the same effect as fasting, suggesting that monocyte frequency is responsive to energy status. This was mediated via hepatocyte peroxisome proliferator-activated receptor-α, a target of AMPK which is highly expressed in the liver. This shows that energy sensing in the liver has a significant influence on the immune system, and is mediated by a reduction in CCL2 expression. Finally, previous observations that chronic inflammatory diseases respond to fasting or hypocalorific diets was confirmed in a model of multiple sclerosis where fasting reduced inflammation and improved signs of disease, but without a detrimental effect on an acute response to pathogens. These data describe a central role for the liver in the connection between dietary intake, energy metabolism and immunity, and again highlight the CCL2/CCR2 axis as a mediator of carbohydrate-induced inflammation. The role of careful fasting or limiting carbohydrate intake in the management of chronic inflammatory disease is highly relevant to many areas of gastroenterology.