Abstract
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.
Highlights
Obesity is a leading risk factor for cardiovascular disease (CVD) mortality and morbidity (Van Gaal et al 2006), independently associated with the progression of coronary artery disease (Al Suwaidi et al 2001)
We showed that the primary mechanisms for exercise-induced improvement of vascular function were enhanced endothelial NO synthase (eNOS)-mediated nitric oxide (NO) production and reduced oxidative stress and inflammatory signaling in vascular endothelium (Lee et al 2011; Park et al 2012)
The current results demonstrate that voluntary running reduces OÁ2À production in coronary arterioles of high-fat diet (HFD) mice (Fig. 5A) building on our previous study using the same primordial prevention concept which reported that chronic voluntary running normalizes plasma insulin, glucose, and OÁ2À generation in HFD (Park et al 2012)
Summary
Obesity is a leading risk factor for cardiovascular disease (CVD) mortality and morbidity (Van Gaal et al 2006), independently associated with the progression of coronary artery disease (Al Suwaidi et al 2001). Excess caloric intake and physically inactive lifestyles are considered as important factors to contribute to obesity (Hill et al 2012). Endothelial dysfunction, mainly affected by reduced nitric oxide (NO) bioavailability and increased oxidative stress, is an important predictor of CVD. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, NOX, family-derived superoxide (OÁ2À) generation (Konior et al 2014) impairs endothelium-dependent vasodilation by reduced endothelial NO synthase (eNOS)-mediated NO formation Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
