Effects of an exogenous ketone ester using multi-omics in skeletal muscle of aging C57BL/6J male mice.

Autor: Roberts BM; Department of Human Studies, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL, United States., Deemer SE; Department of Kinesiology, Health Promotion, and Recreation, University of North Texas, Denton, TX, United States., Smith DL Jr; Department of Nutrition Sciences, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL, United States., Mobley JA; Department of Anesthesiology and Perioperative Medicine, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL, United States., Musi N; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, United States.; San Antonio Geriatric Research, Education, and Clinical Center, San Antonio, TX, United States., Plaisance EP; Department of Human Studies, Division of Molecular and Translational Biomedicine, University of Alabama at Birmingham, Birmingham, AL, United States.
Jazyk: angličtina
Zdroj: Frontiers in nutrition [Front Nutr] 2022 Nov 15; Vol. 9, pp. 1041026. Date of Electronic Publication: 2022 Nov 15 (Print Publication: 2022).
DOI: 10.3389/fnut.2022.1041026
Abstrakt: Exogenous ketone ester supplementation provides a means to increase circulating ketone concentrations without the dietary challenges imposed by ketogenic diets. Our group has shown that oral R,S-1,3, butanediol diacetoacetate (BD-AcAc 2 ) consumption results in body weight loss or maintenance with moderate increases in circulating ketones. We have previously shown a diet consisting of 25% BD-AcAc 2 can maintain lean body mass (LBM) and induce fat mass (FM) loss in young, healthy male mice, but the underlying mechanisms are still unknown. Therefore, the purpose of this study was to determine if a diet consisting of 25% BD-AcAc 2 (ketone ester, KE) would alter body composition, transcriptional regulation, the proteome, and the lipidome of skeletal muscle in aged mice. We hypothesized that the KE group would remain weight stable with improvements in body composition compared to controls, resulting in a healthy aging phenotype. Male C57BL/6J mice ( n = 16) were purchased from Jackson Laboratories at 72 weeks of age. After 1 week of acclimation, mice were weighed and randomly assigned to one of two groups ( n = 8 per group): control (CON) or KE. A significant group by time interaction was observed for body weight ( P < 0.001), with KE fed mice weighing significantly less than CON. FM increased over time in the control group but was unchanged in the KE group. Furthermore, LBM was not different between CON and KE mice despite KE mice weighing less than CON mice. Transcriptional analysis of skeletal muscle identified 6 genes that were significantly higher and 21 genes that were significantly lower in the KE group compared to CON. Lipidomic analysis of skeletal muscle identified no differences between groups for any lipid species, except for fatty acyl chains in triacylglycerol which was 46% lower in the KE group. Proteomics analysis identified 44 proteins that were different between groups, of which 11 were lower and 33 were higher in the KE group compared to CON. In conclusion, 72-week-old male mice consuming the exogenous KE, BD-AcAc 2 , had lower age-related gains in body weight and FM compared to CON mice. Furthermore, transcriptional and proteomics data suggest a signature in skeletal muscle of KE-treated mice consistent with markers of improved skeletal muscle regeneration, improved electron transport chain utilization, and increased insulin sensitivity.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Roberts, Deemer, Smith, Mobley, Musi and Plaisance.)
Databáze: MEDLINE
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