Oral Supplementation with the Short-Chain Fatty Acid Acetate Ameliorates Age-Related Arterial Dysfunction in Mice.
Abigail G Longtine, Nathan T Greenberg, Antonio Gonzalez, Alexandra Lindquist, Nicholas S VanDongen, Sophia A Mahoney, Gibraan Rahman, Zachary S Clayton, Brian P Ziemba, Katelyn R Ludwig, Michael E Widlansky, Rob Knight, Douglas R Seals, Vienna E Brunt
Author Information
Abigail G Longtine: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Nathan T Greenberg: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Antonio Gonzalez: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Alexandra Lindquist: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Nicholas S VanDongen: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Sophia A Mahoney: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Gibraan Rahman: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Zachary S Clayton: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Brian P Ziemba: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Katelyn R Ludwig: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Michael E Widlansky: Departments of Medicine and Pharmacology and the Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Rob Knight: Department of Pediatrics, University of California San Diego, La Jolla, CA, USA.
Douglas R Seals: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Vienna E Brunt: Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO, USA.
Adverse changes in the gut microbiome with aging are an emerging mediator of arterial dysfunction, which contributes to cardiovascular disease (CVD) development. We investigated the therapeutic potential of enhancing the bioavailability of gut-derived short-chain fatty acids (SCFAs; produced from dietary fiber) for improving age-related arterial dysfunction. We performed gut microbial whole-genome sequencing in young (3 months) versus old (24 months) male C57BL/6N mice to explore changes in bacterial taxonomic abundance and functional pathways with aging and relations to arterial function. We then supplemented young and old mice with the SCFA acetate in drinking water versus controls and versus a high-fiber diet for 8-10 weeks to test the effects of these interventions on vascular function and explore potential mechanisms. Of the various differences in the gut microbiomes of old mice, lower SCFA-producing capacity (taxonomic abundance and functional pathways) stood out as a key feature related to worse arterial function after adjusting for age. Acetate supplementation and a high-fiber diet reversed ~30% of the age-related increase in aortic pulse wave velocity (stiffness) and fully restored carotid artery endothelium-dependent dilation (endothelial function) to young levels. Acetate and a high-fiber diet reduced age-related increases in systemic inflammation. We also found that improvements in endothelial function were likely mediated by suppressed early growth response-1 signaling using innovative siRNA-based knockdown in isolated arteries. There were no effects of the interventions in young mice. Acetate supplementation was comparably effective for ameliorating arterial dysfunction with aging as a high-fiber diet and thus shows promise for reducing CVD risk in older adults.
References
Circ Res. 2018 Oct 12;123(9):1091-1102
[PMID: 30355158]
