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

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title = "N1-methylnicotinamide is a signalling molecule produced in skeletal muscle coordinating energy metabolism",
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 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.",
author = "Kristoffer Str{\"o}m and David Morales-Alamo and Filip Ottosson and Anna Edlund and Line Hjort and J{\"o}rgensen, {Sine W.} and Peter Almgren and Yuedan Zhou and Marcos Martin-Rincon and Carl Ekman and Alberto P{\'e}rez-L{\'o}pez and Ola Ekstr{\"o}m and Ismael Perez-Suarez and Markus Mattiasson and {De Pablos-Velasco}, Pedro and Nikolay Oskolkov and Emma Ahlqvist and Nils Wierup and Lena Eliasson and Allan Vaag and Leif Groop and Stenkula, {Karin G.} and C{\'e}line Fernandez and Calbet, {Jose A.L.} and Holmberg, {Hans Christer} and Ola Hansson",
year = "2018",
month = dec,
day = "1",
doi = "10.1038/s41598-018-21099-1",
language = "English",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",