title: Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance.
abstract: OBJECTIVE
  Methionine-restricted (MR) rats, which are lean and insulin sensitive, have low serum total cysteine (tCys) and taurine and decreased hepatic expression and activity indices of stearoyl-coenzyme A desaturase-1 (SCD1). These effects are partly or completely reversed by cysteine supplementation. We investigated whether reversal of MR phenotypes can be achieved by other sulfur compounds, namely taurine or N-acetylcysteine (NAC).
  
  
  METHODS
  MR and control-fed (CF) rats were supplemented with taurine (0.5%) or NAC (0.5%) for 12weeks. Adiposity, serum sulfur amino acids (SAA), Scd1 gene expression in liver and white adipose tissue, and SCD1 activity indices (calculated from serum fatty acid profile) were monitored.
  
  
  RESULTS
  Taurine supplementation of MR rats did not restore weight gain or hepatic Scd1 expression or indices to CF levels, but further decreased adiposity. Taurine supplementation of CF rats did not affect adiposity, but lowered triglyceridemia. NAC supplementation in MR rats raised tCys and partly or completely reversed MR effects on weight, fat %, Scd1 expression in liver and white adipose tissue, and estimated SCD1 activity. In CF rats, NAC decreased body fat % and lowered SCD1-18 activity index (P<0.001). Serum triglycerides and leptin were over 40% lower in CF+NAC relative to CF rats (P≤0.003 for both). In all groups, change in tCys correlated with change in SCD1-16 index (partial r=0.60, P<0.001) independent of other SAA.
  
  
  CONCLUSIONS
  The results rule out taurine as a mediator of increased adiposity produced by cysteine in MR, and show that NAC, similar to L-cysteine, blocks anti-obesity effects of MR. Our data show that dietary SAA can influence adiposity in part through mechanisms that converge on SCD1 function. This may have implications for understanding and preventing human obesity.
authors.affiliation: Department of Pharmacology, University of Oxford, UK. amany.elshorbagy@pharm.ox.ac.uk
authors.forename: Amany K
authors.initials: AK
authors.lastname: Elshorbagy
authors.forename: Maria
authors.initials: M
authors.lastname: Valdivia-Garcia
authors.forename: Dwight A L
authors.initials: DA
authors.lastname: Mattocks
authors.forename: Jason D
authors.initials: JD
authors.lastname: Plummer
authors.forename: David S
authors.initials: DS
authors.lastname: Orentreich
authors.forename: Norman
authors.initials: N
authors.lastname: Orentreich
authors.forename: Helga
authors.initials: H
authors.lastname: Refsum
authors.forename: Carmen E
authors.initials: CE
authors.lastname: Perrone
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D050154:Adiposity / Q000187:drug effects*; D000596:Amino Acids / Q000097:blood; D000603:Amino Acids, Sulfur / Q000378:metabolism; D000818:Animals; D003545:Cysteine / Q000097:blood; D004032:Diet; D005230:Fatty Acids, Nonesterified / Q000097:blood; D016166:Free Radical Scavengers / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051381:Rats; D011916:Rats, Inbred F344; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000596:Amino Acids; D000603:Amino Acids, Sulfur; D005230:Fatty Acids, Nonesterified; D016166:Free Radical Scavengers; D008055:Lipids; D013654:Taurine; D008715:Methionine; D013230:Stearoyl-CoA Desaturase; D003545:Cysteine; D000111:Acetylcysteine