Nitrate consumption preserves HFD-induced skeletal muscle mitochondrial ADP sensitivity and lysine acetylation: A potential role for SIRT1.

Autor: Brunetta HS; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada; Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, Brazil. Electronic address: henver@unicamp.br., Petrick HL; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada., Momken I; Signaling and Cardiovascular Pathophysiology, UMR-S 1180, Inserm Université Paris-Saclay, France; Université d'Evry Val d'Essonne, France., Handy RM; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada., Pignanelli C; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada., Nunes EA; Department of Physiological Sciences, Federal University of Santa Catarina, Florianópolis, Brazil., Piquereau J; Signaling and Cardiovascular Pathophysiology, UMR-S 1180, Inserm Université Paris-Saclay, France., Mericskay M; Signaling and Cardiovascular Pathophysiology, UMR-S 1180, Inserm Université Paris-Saclay, France., Holloway GP; Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Canada. Electronic address: ghollowa@uoguelph.ca.
Jazyk: angličtina
Zdroj: Redox biology [Redox Biol] 2022 Jun; Vol. 52, pp. 102307. Date of Electronic Publication: 2022 Mar 31.
DOI: 10.1016/j.redox.2022.102307
Abstrakt: Dietary nitrate supplementation, and the subsequent serial reduction to nitric oxide, has been shown to improve glucose homeostasis in several pre-clinical models of obesity and insulin resistance. While the mechanisms remain poorly defined, the beneficial effects of nitrate appear to be partially dependent on AMPK-mediated signaling events, a central regulator of metabolism and mitochondrial bioenergetics. Since AMPK can activate SIRT1, we aimed to determine if nitrate supplementation (4 mM sodium nitrate via drinking water) improved skeletal muscle mitochondrial bioenergetics and acetylation status in mice fed a high-fat diet (HFD: 60% fat). Consumption of HFD induced whole-body glucose intolerance, and within muscle attenuated insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity (higher apparent K m ), submaximal ADP-supported respiration, mitochondrial hydrogen peroxide (mtH 2 O 2 ) production in the presence of ADP and increased cellular protein carbonylation alongside mitochondrial-specific acetylation. Consumption of nitrate partially preserved glucose tolerance and, within skeletal muscle, normalized insulin-induced Akt phosphorylation, mitochondrial ADP sensitivity, mtH 2 O 2 , protein carbonylation and global mitochondrial acetylation status. Nitrate also prevented the HFD-mediated reduction in SIRT1 protein, and interestingly, the positive effects of nitrate ingestion on glucose homeostasis and mitochondrial acetylation levels were abolished in SIRT1 inducible knock-out mice, suggesting SIRT1 is required for the beneficial effects of dietary nitrate. Altogether, dietary nitrate preserves mitochondrial ADP sensitivity and global lysine acetylation in HFD-fed mice, while in the absence of SIRT1, the effects of nitrate on glucose tolerance and mitochondrial acetylation were abrogated.
(Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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