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

Research output: Contribution to journalArticle


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.


  • Kristoffer Ström
  • David Morales-Alamo
  • Line Hjort
  • Sine W. Jörgensen
  • Peter Almgren
  • Yuedan Zhou
  • Marcos Martin-Rincon
  • Carl Ekman
  • Alberto Pérez-López
  • Ismael Perez-Suarez
  • Markus Mattiasson
  • Pedro De Pablos-Velasco
  • Nikolay Oskolkov
  • Jose A.L. Calbet
  • Hans Christer Holmberg
External organisations
  • Mid Sweden University, Östersund
  • University of Las Palmas de Gran Canaria
  • Copenhagen University Hospital
  • University of Alcalá
  • University of Helsinki
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Article number3016
JournalScientific Reports
Issue number1
Publication statusPublished - 2018 Dec 1
Publication categoryResearch