Effect of taurine and N-acetylcysteine on methionine restriction-mediated adiposity resistance

Abstract 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 su...

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Published in:Metabolism, clinical and experimental clinical and experimental, 2013-04, Vol.62 (4), p.509-517
Main Authors: Elshorbagy, Amany K, Valdivia-Garcia, Maria, Mattocks, Dwight A.L, Plummer, Jason D, Orentreich, David S, Orentreich, Norman, Refsum, Helga, Perrone, Carmen E
Format: Article
Language:English
Subjects:
Acetylcysteine - pharmacology
Adiposity - drug effects
Amino Acids - blood
Amino Acids, Sulfur - metabolism
Animals
Biological and medical sciences
Cysteine
Cysteine - blood
Diet
Endocrinology & Metabolism
Fatty acid profile
Fatty Acids, Nonesterified - blood
Feeding. Feeding behavior
Free Radical Scavengers - pharmacology
Fundamental and applied biological sciences. Psychology
Gene Expression Regulation, Enzymologic - drug effects
Glutathione
Lipids - blood
Male
Methionine - deficiency
Rats
Rats, Inbred F344
Stearoyl coenzyme A desaturase
Stearoyl-CoA Desaturase - biosynthesis
Stearoyl-CoA Desaturase - genetics
Stearoyl-CoA Desaturase - metabolism
Sulfur amino acids
Taurine - pharmacology
Vertebrates: anatomy and physiology, studies on body, several organs or systems
Weight Gain - drug effects
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Summary:Abstract 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.
ISSN:0026-0495
1532-8600
DOI:10.1016/j.metabol.2012.10.005