Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity. / Basse, Astrid L.; Agerholm, Marianne; Farup, Jean; Dalbram, Emilie; Nielsen, Joachim; Ørtenblad, Niels; Altıntaş, Ali; Ehrlich, Amy M.; Krag, Thomas; Bruzzone, Santina; Dall, Morten; de Guia, Roldan M.; Jensen, Jonas B.; Møller, Andreas B.; Karlsen, Anders; Kjær, Michael; Barrès, Romain; Vissing, John; Larsen, Steen; Jessen, Niels; Treebak, Jonas T.

In: Molecular Metabolism, Vol. 53, 101271, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Basse, AL, Agerholm, M, Farup, J, Dalbram, E, Nielsen, J, Ørtenblad, N, Altıntaş, A, Ehrlich, AM, Krag, T, Bruzzone, S, Dall, M, de Guia, RM, Jensen, JB, Møller, AB, Karlsen, A, Kjær, M, Barrès, R, Vissing, J, Larsen, S, Jessen, N & Treebak, JT 2021, 'Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity', Molecular Metabolism, vol. 53, 101271. https://doi.org/10.1016/j.molmet.2021.101271

APA

Basse, A. L., Agerholm, M., Farup, J., Dalbram, E., Nielsen, J., Ørtenblad, N., Altıntaş, A., Ehrlich, A. M., Krag, T., Bruzzone, S., Dall, M., de Guia, R. M., Jensen, J. B., Møller, A. B., Karlsen, A., Kjær, M., Barrès, R., Vissing, J., Larsen, S., ... Treebak, J. T. (2021). Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity. Molecular Metabolism, 53, [101271]. https://doi.org/10.1016/j.molmet.2021.101271

Vancouver

Basse AL, Agerholm M, Farup J, Dalbram E, Nielsen J, Ørtenblad N et al. Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity. Molecular Metabolism. 2021;53. 101271. https://doi.org/10.1016/j.molmet.2021.101271

Author

Basse, Astrid L. ; Agerholm, Marianne ; Farup, Jean ; Dalbram, Emilie ; Nielsen, Joachim ; Ørtenblad, Niels ; Altıntaş, Ali ; Ehrlich, Amy M. ; Krag, Thomas ; Bruzzone, Santina ; Dall, Morten ; de Guia, Roldan M. ; Jensen, Jonas B. ; Møller, Andreas B. ; Karlsen, Anders ; Kjær, Michael ; Barrès, Romain ; Vissing, John ; Larsen, Steen ; Jessen, Niels ; Treebak, Jonas T. / Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity. In: Molecular Metabolism. 2021 ; Vol. 53.

Bibtex

@article{b3079791dda942dc8ed150a7f76ba686,
title = "Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity",
abstract = "Objective: NAD+ is a co-factor and substrate for enzymes maintaining energy homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT) controls NAD+ synthesis, and in skeletal muscle, NAD+ is essential for muscle integrity. However, the underlying molecular mechanisms by which NAD+ synthesis affects muscle health remain poorly understood. Thus, the objective of the current study was to delineate the role of NAMPT-mediated NAD+ biosynthesis in skeletal muscle development and function. Methods: To determine the role of Nampt in muscle development and function, we generated skeletal muscle-specific Nampt KO (SMNKO) mice. We performed a comprehensive phenotypic characterization of the SMNKO mice, including metabolic measurements, histological examinations, and RNA sequencing analyses of skeletal muscle from SMNKO mice and WT littermates. Results: SMNKO mice were smaller, with phenotypic changes in skeletal muscle, including reduced fiber area and increased number of centralized nuclei. The majority of SMNKO mice died prematurely. Transcriptomic analysis identified that the gene encoding the mitochondrial permeability transition pore (mPTP) regulator Cyclophilin D (Ppif) was upregulated in skeletal muscle of SMNKO mice from 2 weeks of age, with associated increased sensitivity of mitochondria to the Ca2+-stimulated mPTP opening. Treatment of SMNKO mice with the Cyclophilin D inhibitor, Cyclosporine A, increased membrane integrity, decreased the number of centralized nuclei, and increased survival. Conclusions: Our study demonstrates that NAMPT is crucial for maintaining cellular Ca2+ homeostasis and skeletal muscle development, which is vital for juvenile survival.",
keywords = "Cyclophilin D, Mitochondrial permeability transition pore (mPTP), Myopathy, NAD, Nicotinamide riboside, Sarcopenia",
author = "Basse, {Astrid L.} and Marianne Agerholm and Jean Farup and Emilie Dalbram and Joachim Nielsen and Niels {\O}rtenblad and Ali Altınta{\c s} and Ehrlich, {Amy M.} and Thomas Krag and Santina Bruzzone and Morten Dall and {de Guia}, {Roldan M.} and Jensen, {Jonas B.} and M{\o}ller, {Andreas B.} and Anders Karlsen and Michael Kj{\ae}r and Romain Barr{\`e}s and John Vissing and Steen Larsen and Niels Jessen and Treebak, {Jonas T.}",
note = "Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
doi = "10.1016/j.molmet.2021.101271",
language = "English",
volume = "53",
journal = "Molecular Metabolism",
issn = "2212-8778",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Nampt controls skeletal muscle development by maintaining Ca2+ homeostasis and mitochondrial integrity

AU - Basse, Astrid L.

AU - Agerholm, Marianne

AU - Farup, Jean

AU - Dalbram, Emilie

AU - Nielsen, Joachim

AU - Ørtenblad, Niels

AU - Altıntaş, Ali

AU - Ehrlich, Amy M.

AU - Krag, Thomas

AU - Bruzzone, Santina

AU - Dall, Morten

AU - de Guia, Roldan M.

AU - Jensen, Jonas B.

AU - Møller, Andreas B.

AU - Karlsen, Anders

AU - Kjær, Michael

AU - Barrès, Romain

AU - Vissing, John

AU - Larsen, Steen

AU - Jessen, Niels

AU - Treebak, Jonas T.

N1 - Publisher Copyright: © 2021 The Author(s)

PY - 2021

Y1 - 2021

N2 - Objective: NAD+ is a co-factor and substrate for enzymes maintaining energy homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT) controls NAD+ synthesis, and in skeletal muscle, NAD+ is essential for muscle integrity. However, the underlying molecular mechanisms by which NAD+ synthesis affects muscle health remain poorly understood. Thus, the objective of the current study was to delineate the role of NAMPT-mediated NAD+ biosynthesis in skeletal muscle development and function. Methods: To determine the role of Nampt in muscle development and function, we generated skeletal muscle-specific Nampt KO (SMNKO) mice. We performed a comprehensive phenotypic characterization of the SMNKO mice, including metabolic measurements, histological examinations, and RNA sequencing analyses of skeletal muscle from SMNKO mice and WT littermates. Results: SMNKO mice were smaller, with phenotypic changes in skeletal muscle, including reduced fiber area and increased number of centralized nuclei. The majority of SMNKO mice died prematurely. Transcriptomic analysis identified that the gene encoding the mitochondrial permeability transition pore (mPTP) regulator Cyclophilin D (Ppif) was upregulated in skeletal muscle of SMNKO mice from 2 weeks of age, with associated increased sensitivity of mitochondria to the Ca2+-stimulated mPTP opening. Treatment of SMNKO mice with the Cyclophilin D inhibitor, Cyclosporine A, increased membrane integrity, decreased the number of centralized nuclei, and increased survival. Conclusions: Our study demonstrates that NAMPT is crucial for maintaining cellular Ca2+ homeostasis and skeletal muscle development, which is vital for juvenile survival.

AB - Objective: NAD+ is a co-factor and substrate for enzymes maintaining energy homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT) controls NAD+ synthesis, and in skeletal muscle, NAD+ is essential for muscle integrity. However, the underlying molecular mechanisms by which NAD+ synthesis affects muscle health remain poorly understood. Thus, the objective of the current study was to delineate the role of NAMPT-mediated NAD+ biosynthesis in skeletal muscle development and function. Methods: To determine the role of Nampt in muscle development and function, we generated skeletal muscle-specific Nampt KO (SMNKO) mice. We performed a comprehensive phenotypic characterization of the SMNKO mice, including metabolic measurements, histological examinations, and RNA sequencing analyses of skeletal muscle from SMNKO mice and WT littermates. Results: SMNKO mice were smaller, with phenotypic changes in skeletal muscle, including reduced fiber area and increased number of centralized nuclei. The majority of SMNKO mice died prematurely. Transcriptomic analysis identified that the gene encoding the mitochondrial permeability transition pore (mPTP) regulator Cyclophilin D (Ppif) was upregulated in skeletal muscle of SMNKO mice from 2 weeks of age, with associated increased sensitivity of mitochondria to the Ca2+-stimulated mPTP opening. Treatment of SMNKO mice with the Cyclophilin D inhibitor, Cyclosporine A, increased membrane integrity, decreased the number of centralized nuclei, and increased survival. Conclusions: Our study demonstrates that NAMPT is crucial for maintaining cellular Ca2+ homeostasis and skeletal muscle development, which is vital for juvenile survival.

KW - Cyclophilin D

KW - Mitochondrial permeability transition pore (mPTP)

KW - Myopathy

KW - NAD

KW - Nicotinamide riboside

KW - Sarcopenia

U2 - 10.1016/j.molmet.2021.101271

DO - 10.1016/j.molmet.2021.101271

M3 - Journal article

C2 - 34119711

AN - SCOPUS:85108978816

VL - 53

JO - Molecular Metabolism

JF - Molecular Metabolism

SN - 2212-8778

M1 - 101271

ER -

ID: 273702264