Accumulating evidence suggests that the type and quan- tity of dietary proteins affects body weight. In humans, high-protein diets and leucine supplementation promote weight loss, improve body composition, and decrease insu-

Accumulating evidence suggests that the type and quantity of dietary proteins affects body weight. In humans, high-protein diets and leucine supplementation promote weight loss, improve body composition, and decrease insulin when used in weight loss programs ( 1 ). These effects may be related to enhanced satiety and increased energy expenditure ( 2 ). On the other hand, high habitual protein intake is epidemiologically associated with greater body mass index (BMI) ( 3 ) and body fat ( 3, 4 ). Rats fed high-protein diets develop insulin resistance ( 5 ), and type 1 diabetic patients on a high-protein diet have reduced insulin sensitivity compared with those with lower protein intake ( 6 ). Specifi cally, higher intake of animal-derived protein is associated in large cross-sectional studies with greater BMI and higher prevalence of obesity ( 7–9 ). Prospective studies show that subjects with higher animal protein consumption gain more weight over time ( 10 ) and are more likely to develop diabetes ( 11, 12 ). The possibility that specifi c amino acid constituents mediate metabolic effects of different protein types is likely but has not been clearly documented. Methionine, an essential sulfur-containing amino acid mainly ingested in animal-derived foods ( 13 ), is a potential mediator of adverse effects of excess animal protein intake ( 14 ), and, at high intake levels, is associated with Abstract Stearoyl-CoA desaturase-1 (SCD1) is a key enzyme in fatty acid and energy metabolism, but little is known about its nutritional regulation. Dietary methionine restriction in rats decreases hepatic Scd1 mRNA and protein, increases energy expenditure, and decreases fat-pad mass/ body-weight% (FM/BW%). In humans, plasma concentrations of the methionine product, cysteine, are associated with obesity. To determine which consequences of methioninerestriction are mediated by decreased cysteine availability, we monitored obesity-related variables in 4 dietary groups for 12 weeks: control-fed (CF), methionine-restricted (MR), MR supplemented with 0.5% L -cysteine (MR+Cys) and CF+Cys rats. MR lowered weight gain and FM/BW% despite higher food intake/weight than CF, and lowered serum cysteine. Hepatic Scd1 expression was decreased, with decreased serum SCD1 activity indices (calculated from serum fatty acid profi le), decreased serum insulin, leptin and triglycerides, and higher adiponectin. Cysteine supplementation (MR+Cys) essentially reversed all these phenotypes and raised serum cysteine but not methionine to CF levels. Adding extra cysteine to control diet (CF+Cys) increased serum taurine but did not affect serum cysteine, lipids, proteins, or total weight gain. FM/BW% and serum leptin were modestly decreased. Our results indicate that antiobesity effects of MR are caused by low cysteine and that dietary sulfur amino acid composition contributes to SCD1 regulation. —Elshorbagy, A. K., M. Valdivia-Garcia, D. A. L. Mattocks, J. D. Plummer, A. D. Smith, C. A. Drevon, H. Refsum, and C. E. Perrone. Cysteine supplementation reverses methionine restriction effects on rat adiposity: signifi cance of stearoyl-coenzyme A desaturase. J. Lipid Res . 2011. 52: 104–112.