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

• Published in: Scientific reports Vol. 8; no. 1; pp. 1 - 12
• Main Authors: Ström, Kristoffer, Morales-Alamo, David, Ottosson, Filip, Edlund, Anna, Hjort, Line, Jörgensen, Sine W., Almgren, Peter, Zhou, Yuedan, Martin-Rincon, Marcos, Ekman, Carl, Pérez-López, Alberto, Ekström, Ola, Perez-Suarez, Ismael, Mattiasson, Markus, de Pablos-Velasco, Pedro, Oskolkov, Nikolay, Ahlqvist, Emma, Wierup, Nils, Eliasson, Lena, Vaag, Allan, Groop, Leif, Stenkula, Karin G., Fernandez, Céline, Calbet, Jose A. L., Holmberg, Hans-Christer, Hansson, Ola
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.02.2018; Nature Publishing Group
• Subjects: 101/58; 38; 38/90; 631/208/199; 692/163/2743; 82/1; 82/16; 82/29; Adipose tissue; Body weight loss; Carbohydrate metabolism; Clinical Medicine; Dietary restrictions; Endocrinology and Diabetes; Endokrinologi och diabetes; Energy metabolism; Event-related potentials; Fasting; Fat metabolism; Glucagon; Humanities and Social Sciences; Insulin; Insulin secretion; Klinisk medicin; Lipolysis; Medical and Health Sciences; Medicin och hälsovetenskap; Metabolism; Methyltransferase; multidisciplinary; Musculoskeletal system; Myotubes; N-Methyltransferase; Nicotinamide; Nicotinamide N-methyltransferase; Obesity; Science; Science (multidisciplinary); Secretion; Skeletal muscle
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-21099-1

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 1 -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.