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N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism

Ström, Kristoffer LU ; Morales-Alamo, David ; Ottosson, Filip LU ; Edlund, Anna LU ; Hjort, Line ; Jörgensen, Sine W. ; Almgren, Peter LU ; Zhou, Yuedan LU ; Martin-Rincon, Marcos and Ekman, Carl LU , et al. (2018) In Scientific Reports 8(1).
Abstract

Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels... (More)

Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N1-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
8
issue
1
article number
3016
publisher
Nature Publishing Group
external identifiers
  • scopus:85042133592
  • pmid:29445118
ISSN
2045-2322
DOI
10.1038/s41598-018-21099-1
language
English
LU publication?
yes
id
bde7ce36-db9b-4b2a-a2e3-fffdb3fbf67d
date added to LUP
2018-03-02 15:00:56
date last changed
2023-04-08 08:11:27
@article{bde7ce36-db9b-4b2a-a2e3-fffdb3fbf67d,
  abstract     = {{<p>Obesity is a major health problem, and although caloric restriction and exercise are successful strategies to lose adipose tissue in obese individuals, a simultaneous decrease in skeletal muscle mass, negatively effects metabolism and muscle function. To deeper understand molecular events occurring in muscle during weight-loss, we measured the expressional change in human skeletal muscle following a combination of severe caloric restriction and exercise over 4 days in 15 Swedish men. Key metabolic genes were regulated after the intervention, indicating a shift from carbohydrate to fat metabolism. Nicotinamide N-methyltransferase (NNMT) was the most consistently upregulated gene following the energy-deficit exercise. Circulating levels of N<sup>1</sup>-methylnicotinamide (MNA), the product of NNMT activity, were doubled after the intervention. The fasting-fed state was an important determinant of plasma MNA levels, peaking at ~18 h of fasting and being lowest ~3 h after a meal. In culture, MNA was secreted by isolated human myotubes and stimulated lipolysis directly, with no effect on glucagon or insulin secretion. We propose that MNA is a novel myokine that enhances the utilization of energy stores in response to low muscle energy availability. Future research should focus on applying MNA as a biomarker to identify individuals with metabolic disturbances at an early stage.</p>}},
  author       = {{Ström, Kristoffer and Morales-Alamo, David and Ottosson, Filip and Edlund, Anna and Hjort, Line and Jörgensen, Sine W. and Almgren, Peter and Zhou, Yuedan and Martin-Rincon, Marcos and Ekman, Carl and Pérez-López, Alberto and Ekström, Ola and Perez-Suarez, Ismael and Mattiasson, Markus and De Pablos-Velasco, Pedro and Oskolkov, Nikolay and Ahlqvist, Emma and Wierup, Nils and Eliasson, Lena and Vaag, Allan and Groop, Leif and Stenkula, Karin G. and Fernandez, Céline and Calbet, Jose A.L. and Holmberg, Hans Christer and Hansson, Ola}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{12}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{N<sup>1</sup>-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism}},
  url          = {{http://dx.doi.org/10.1038/s41598-018-21099-1}},
  doi          = {{10.1038/s41598-018-21099-1}},
  volume       = {{8}},
  year         = {{2018}},
}