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Assessment of the Metabolic Effects of Isocaloric 2:1 Intermittent Fasting in Mice
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Intermittent fasting inhibits platelet activation and thrombosis through the intestinal metabolite

Zhiyong Qi1,2, Luning Zhou1,2, Shimo Dai1,2

  • 1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, 180 Fenglin Road, Shanghai 200032, China.

Life Metabolism
|March 13, 2025
PubMed

Insights

Intermittent fasting (IF) reduces platelet activation and thrombosis risk. This effect is mediated by gut bacteria producing indole-3-propionic acid (IPA), which targets platelet PXR signaling pathways.

Area of Science:

  • Cardiovascular Research
  • Metabolic Health
  • Microbiome Research

Background:

  • Platelet hyperreactivity is a key factor in thrombotic events like heart attack and stroke.
  • Current antiplatelet therapies leave residual ischemic risk.
  • The impact of intermittent fasting (IF) on platelet activation is not well understood.

Purpose of the Study:

  • To investigate the effect of IF on platelet activation and thrombosis.
  • To elucidate the underlying mechanisms of IF's action on platelets.
  • To assess IF's potential to alleviate ischemia/reperfusion injury.

Main Methods:

  • Studied IF's impact on platelet activation in patients with coronary artery disease and in apolipoprotein E knockout mice.
  • Analyzed the role of gut microbiota and indole-3-propionic acid (IPA) in IF's effects.
  • Investigated the molecular targets of IPA in platelet signaling, including pregnane X receptor (PXR) and downstream pathways.

Main Results:

  • Intermittent fasting significantly inhibited platelet activation and thrombosis in both human patients and animal models.
  • IF increased intestinal flora production of indole-3-propionic acid (IPA).
  • Elevated IPA directly reduced platelet activation by binding to platelet PXR, suppressing Src/Lyn/Syk and LAT/PLCγ/PKC/Ca2+ signaling.
  • IF treatment alleviated myocardial and cerebral ischemia/reperfusion injury in mice.

Conclusions:

  • Intermittent fasting mitigates platelet activation and thrombosis risk in coronary atherosclerosis.
  • Enhanced gut microbial production of IPA is a key mediator of IF's antiplatelet effects.
  • IPA's activation of platelet PXR signaling pathways offers a novel therapeutic target for reducing thrombotic risk.

Keywords:
PXRarterial thrombosisindole-3-propionateintermittent fastingplatelet activation

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