Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance Amany K. Elshorbagy a, b, ⁎ , Maria Valdivia-Garcia a , Dwight A.L. Mattocks c , Jason D. Plummer c , David S. Orentreich c , Norman Orentreich c , Helga Refsum a, d, 1 , Carmen E. Perrone c , 1 a Department of Pharmacology, University of Oxford, UK b Department of Physiology, Faculty of Medicine, University of Alexandria, Egypt c Cell Biology Laboratory, Orentreich Foundation for the Advancement of Science, Inc., Cold Spring-on-Hudson, New York, USA d Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Norway ARTICLE INFO ABSTRACT Article history: Received 22 June 2012 Accepted 9 October 2012 Objectives. 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 12 weeks. 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. Conclusion. 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. © 2013 Elsevier Inc. All rights reserved. Keywords: Glutathione Cysteine Sulfur amino acids Stearoyl coenzyme A desaturase Fatty acid profile METABOLISM CLINICAL AND EXPERIMENTAL 62 (2013) 509 – 517 Abbreviations: CF, Control-fed; MR, Methionine restriction/restricted; NAC, N-acetylcysteine; SAA, Sulfur amino acids; SCD1, Stearoyl- coenzyme A desaturase-1; tCys, Total cysteine; tGSH, Total glutathione; tHcy, Total homocysteine. ⁎ Corresponding author. Department of Pharmacology, University of Oxford, Mansfield Road, OX1 3QT Oxford, UK. Tel.: + 44 1865 271877. E-mail address: amany.elshorbagy@pharm.ox.ac.uk (A.K. Elshorbagy). 1 Joint senior authors. 0026-0495/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.metabol.2012.10.005 Available online at www.sciencedirect.com Metabolism www.metabolismjournal.com