Key result
Voluntary running preserves ACh-induced vasodilation in high-fat diet-fed mice by restoring adiponectin and NO production.
Why the study?
Physical inactivity is a major cause of obesity-associated cardiovascular diseases, prompting investigation into whether voluntary running protects against vascular dysfunction across different vascular beds in diet-induced obesity.
Does voluntary running improve endothelial function in high-fat diet-induced obese mice?
RCT
Randomly assigned
Does voluntary running improve endothelial function in high-fat diet-induced obese mice?
Voluntary running protects against high-fat diet-induced endothelial dysfunction in mice via mechanisms involving eNOS, NLRP3 inflammasome, and adiponectin signaling.
Supports exercise protection against obesity-related endothelial dysfunction in mice; leaves open human translation.
Background: Obesity is associated with various cardiovascular diseases, and physical inactivity is one of the major causes of this pathology. This study investigated the protective effects of voluntary running on vascular dysfunction in different vascular beds, mesenteric arteries and the aorta, in the context of high-fat diet (HFD)-induced obesity and its potential underlying mechanisms. Methods: C57BL/6J male mice were randomly assigned into four groups: (1) sedentary low-fat diet (LF-SED), (2) LF diet with free access to a voluntary running wheel (LF-RUN), (3) sedentary high-fat diet (HF-SED; 45% of calories from fat), and (4) HF-RUN. Endothelium-dependent (acetylcholine, ACh-induced) and endothelium-independent (Sodium Nitroprusside, SNP-induced) vasodilation were assessed using isolated, pressurized mesenteric arteries. To determine the effects of voluntary running on the inflammasome-related signaling pathways, adiponectin, and nitric oxide (NO), quantified these factors in the mouse aorta and mesenteric artery using western blotting, RT-qPCR, and immunohistochemistry. Results: ACh-induced vasodilation was significantly reduced in the mesenteric arteries of HF-SED mice compared to LF-SED mice but was preserved in HF-RUN mice. This enhanced ACh-induced vasodilation in HF-RUN and LF-SED was abolished by pre-incubation with the NOS inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) or the UCP2 inhibitor, Genipin. Voluntary running normalized HFD-induced reductions in p-eNOS, adiponectin receptor of mesenteric arteries. Voluntary running decreased cleaved caspase-1 and IL-1β in the aortic endothelium of HF-fed mice. HF-RUN restored the diet-induced decrease of endothelial adiponectin expression and NO production compared to HF-SED. Conclusion: Physical activity protects against the endothelial dysfunctions of different vascular beds in high-fat diet-induced obesity via multiple mechanisms, including eNOS, NLRP3 inflammasome, and adiponectin signaling. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
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Park et al. (2026) conducted an RCT in High-fat diet-induced obesity and vascular dysfunction. Voluntary running vs. Sedentary was evaluated on Endothelium-dependent (ACh-induced) and endothelium-independent (SNP-induced) vasodilation. Voluntary running preserved ACh-induced vasodilation in high-fat diet-fed mice and restored endothelial adiponectin expression and NO production compared to sedentary controls.
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