Physical activity protects NLRP3 inflammasome-associated coronary vascular dysfunction in obese mice

Physiol Rep. 2018 Jun;6(12):e13738. doi: 10.14814/phy2.13738.


Activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome mediates the release of pro-inflammatory cytokine interleukin (IL)-1β and thereby plays a pivotal role in the inflammatory response in vascular pathology. An active lifestyle has beneficial effects on inflammation-associated vascular dysfunction in obesity. However, it remains unclear how physical activity regulates NLRP3 inflammasome-mediated vascular dysfunction in obesity. Therefore, we explored the protective effect of physical activity on NLRP3 inflammasome-associated vascular dysfunction in mouse hearts, and the potential underlying mechanisms. C57BL/6J male mice were randomly divided into four groups: (1) control low-fat diet (LF-SED), (2) LF diet with free access to a voluntary running wheel (LF-RUN), (3) high-fat diet (HF-SED; 45% of calories from fat), and (4) HF-RUN. We examined NLRP3 inflammasome-related signaling pathways, nitric oxide (NO) signaling, and oxidative stress in coronary arterioles to test effects of HFD and physical activity. Voluntary running reduced NLRP3 inflammasome and its downstream effects, caspase-1 and IL-1β in coronary arteriole endothelium of obese mice in immunofluorescence staining. HF-RUN attenuated HFD-dependent endothelial NO synthase (eNOS) reduction and thus increased NO production compared to HF-SED. HFD elevated intracellular superoxide production in coronary arterioles while voluntary running ameliorated oxidative stress. Our findings provide the first evidence that voluntary running attenuates endothelial NLRP3 inflammasome activation in coronary arterioles of HFD feeding mice. Results further suggest that voluntary running improves obesity-induced vascular dysfunction by preserved NO bioavailability via restored expression of eNOS and reduced oxidative stress.

Keywords: Diet-induced obesity; inflammation; vascular function; voluntary running.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterioles / physiopathology
  • Coronary Artery Disease / etiology*
  • Coronary Artery Disease / physiopathology
  • Coronary Vessels / physiopathology*
  • Diet, Fat-Restricted
  • Diet, High-Fat
  • Inflammasomes / physiology*
  • Male
  • Mice, Inbred C57BL
  • Mice, Obese
  • Motor Activity / physiology*
  • NLR Family, Pyrin Domain-Containing 3 Protein / physiology*
  • Nitric Oxide / physiology
  • Obesity / complications*
  • Obesity / physiopathology
  • Oxidative Stress / physiology
  • Signal Transduction / physiology


  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Nitric Oxide