Título
Increasing NAD synthesis in muscle via nicotinamide phosphoribosyltransferase is not sufficient to promote oxidative metabolism
Autor
DAVID FREDERICK
James G. Davis
ANTONIO DAVILA
Beamon Agarwal
SHADAY MICHAN AGUIRRE
Michelle Puchowicz
Eiko Nakamaru-Ogiso
Joseph Baur
Nivel de Acceso
Acceso Abierto
Materias
BIOLOGÍA Y QUÍMICA - (CTI) MEDICINA Y CIENCIAS DE LA SALUD - (CTI) Biología celular - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Metabolismo - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Mitocondria - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamida - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Niacinamida - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Cell biology - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Metabolism - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Mitochondria - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamide - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Niacinamide - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamide-Adenine Dinucleotide (NAD) - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamida-Nucleótido Adenililtransferasa - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamide-Nucleotide Adenylyltransferase - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamida Fosforibosiltransferasa - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) Nicotinamide Phosphoribosyltransferase - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)]) NMN Adenililtransferasa - ([Journal of Biological Chemistry (1083-351X) vol. 290 (2015)])
Resumen o descripción
The NAD biosynthetic precursors nicotinamide mononucleotide and nicotinamide riboside are reported to confer resistance to metabolic defects induced by high fat feeding in part by promoting oxidative metabolism in skeletal muscle. Similar effects are obtained by germ line deletion of major NAD-consuming enzymes, suggesting that the bioavailability of NAD is limiting for maximal oxidative capacity. However, because of their systemic nature, the degree to which these interventions exert cell- or tissue-autonomous effects is unclear. Here, we report a tissue-specific approach to increase NAD biosynthesis only in muscle by overexpressing nicotinamide phosphoribosyltransferase, the rate-limiting enzyme in the salvage pathway that converts nicotinamide to NAD (mNAMPT mice). These mice display a ∼50% increase in skeletal muscle NAD levels, comparable with the effects of dietary NAD precursors, exercise regimens, or loss of poly(ADP-ribose) polymerases yet surprisingly do not exhibit changes in muscle mitochondrial biogenesis or mitochondrial function and are equally susceptible to the metabolic consequences of high fat feeding. We further report that chronic elevation of muscle NAD in vivo does not perturb the NAD/NADH redox ratio. These studies reveal for the first time the metabolic effects of tissue-specific increases in NAD synthesis and suggest that critical sites of action for supplemental NAD precursors reside outside of the heart and skeletal muscle.
Editor
American Society for Biochemistry and Molecular Biology
Fecha de publicación
2015
Tipo de publicación
Artículo
Recurso de información
Formato
Adobe PDF
application/pdf
Fuente
Journal of Biological Chemistry (1083-351X) vol. 290 (2015)
Idioma
Inglés
Relación
http://www.jbc.org/content/290/3/1546.long
Repositorio Orígen
INSTITUTO NACIONAL DE GERIATRIA
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