title: Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance.
abstract: OBJECTIVE
  Nicotinamide-N-methyltransferase (NNMT) was recently shown to be upregulated in mouse models of insulin resistance and obesity. So far, it is unknown whether NNMT is regulated in human disease. We have explored the hypothesis that white adipose tissue (WAT) NNMT expression and plasma 1-methylnicotinamide (MNA) concentration are increased in human insulin resistance and type 2 diabetes.
  
  
  METHODS
  NNMT expression and plasma MNA were analysed in three groups of individuals: (1) 199 patients undergoing abdominal surgery; (2) 60 individuals on a 12-week exercise programme and (3) 55 patients on a two-step bariatric surgery programme.
  
  
  RESULTS
  Patients with manifest type 2 diabetes have a significantly (approximately twofold) higher NNMT expression both in omental and subcutaneous WAT compared with controls. Notably, plasma MNA correlated significantly with WAT NNMT expression in patients with type 2 diabetes (women, r = 0.59, p < 0.001; men, r = 0.61, p < 0.001) but not in healthy control individuals. In insulin-resistant individuals, there was an inverse correlation between insulin sensitivity and plasma MNA (r = 0.44, p = 0.01) or adipose tissue NNMT mRNA (r = 0.64, p < 0.001). The latter association was confirmed in a second cohort (n = 60, r = 0.78, p < 0.001). Interventions improving insulin sensitivity--exercise and bariatric surgery--were associated with a significant (p < 0.001) reduction in WAT NNMT expression. Bariatric surgery was also associated with a significant decrease in plasma MNA.
  
  
  CONCLUSIONS
  We demonstrate that WAT NNMT expression is regulated in human insulin resistance and type 2 diabetes and that plasma MNA correlates with increased tissue NNMT expression and the degree of insulin resistance, making it a potential biomarker for loss of insulin sensitivity.
authors.affiliation: Sanofi Research and Development, Industriepark Hoechst, H824, 65926, Frankfurt am Main, Germany, aimo.kannt@sanofi.com.
authors.forename: Aimo
authors.initials: A
authors.lastname: Kannt
authors.forename: Anja
authors.initials: A
authors.lastname: Pfenninger
authors.forename: Lenore
authors.initials: L
authors.lastname: Teichert
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Arne
authors.initials: A
authors.lastname: Dietrich
authors.forename: Michael R
authors.initials: MR
authors.lastname: Schön
authors.forename: Nora
authors.initials: N
authors.lastname: Klöting
authors.forename: Matthias
authors.initials: M
authors.lastname: Blüher
mesh_terms: D000328:Adult; D000368:Aged; D050110:Bariatric Surgery; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000097:blood; D050903:Nicotinamide N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000097:blood* / Q000175:diagnosis / Q000628:therapy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000201:enzymology*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D009536:Niacinamide; C494406:NNMT protein, human; D050903:Nicotinamide N-Methyltransferase; C024058:N(1)-methylnicotinamide