Cell
Volume 178, Issue 5, 22 August 2019, Pages 1102-1114.e17
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Article
Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool

https://doi.org/10.1016/j.cell.2019.07.050Get rights and content
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Highlights

  • Fasting reduces the numbers of circulating monocytes in healthy humans and mice

  • Fasting also reduces monocyte metabolic and inflammatory activity

  • Hepatic energy-sensing regulates homeostatic monocyte numbers via CCL2 production

  • Fasting improves inflammatory diseases without compromising antimicrobial immunity

Summary

Caloric restriction is known to improve inflammatory and autoimmune diseases. However, the mechanisms by which reduced caloric intake modulates inflammation are poorly understood. Here we show that short-term fasting reduced monocyte metabolic and inflammatory activity and drastically reduced the number of circulating monocytes. Regulation of peripheral monocyte numbers was dependent on dietary glucose and protein levels. Specifically, we found that activation of the low-energy sensor 5′-AMP-activated protein kinase (AMPK) in hepatocytes and suppression of systemic CCL2 production by peroxisome proliferator-activator receptor alpha (PPARα) reduced monocyte mobilization from the bone marrow. Importantly, we show that fasting improves chronic inflammatory diseases without compromising monocyte emergency mobilization during acute infectious inflammation and tissue repair. These results reveal that caloric intake and liver energy sensors dictate the blood and tissue immune tone and link dietary habits to inflammatory disease outcome.

Keywords

Caloric restriction
fasting
metabolism
inflammation
monocyte
liver
AMPK
PPARα
CCL2
inflammatory disease

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