Restriction of methionine in rodent diets increases energy expenditure, limits weight gain, improves insulin sensitivity, and reduces hepatic and circulating lipids. Dietary methionine restriction (MR) is implemented using diets formulated from elemental amino acids (AA) that reduce methionine content to restricted levels of ∼0.17%. However, translational implementation of dietary MR with elemental AA-based diets is confounded by poor palatability. To solve this problem and restrict methionine using intact proteins, casein was subjected to mild oxidation to selectively reduce methionine. Diets were then formulated using oxidized casein, adding back methionine to produce a final concentration of 0.17%. The biological efficacy of dietary MR using the oxidized casein diet was compared to the standard elemental MR diet. Thirty-two, 5-week old male C57BL/6J mice were divided into two groups of 16, with one group receiving the Elemental Control (El Con) diet and the other receiving the Casein Control (Cas Con) diet for 10 days. Thereafter, 8 mice continued on the El Con diet and 8 mice were switched to the Elemental MR (El MR) diet. In similar fashion, 8 mice continued on the Cas Con diet and 8 mice were switched to the Oxidized Casein (Ox Cas) MR diet. Over the subsequent 8 weeks, the behavioral, metabolic, and endocrine responses to the 4 diets were assessed to evaluate the relative efficacy of the 2 approaches to restricting dietary methionine. The El MR diet produced the expected reductions in body weight, fat mass accumulation, fasting insulin, and hepatic and circulating triglycerides, while increasing energy expenditure, serum FGF-21 levels, and weight-specific food consumption. The Ox Cas MR diet produced increases and decreases in each of these variables that paralleled the effects of the El MR diet. Collectively, these findings demonstrate that dietary MR can be effectively implemented using casein after selective oxidative reduction of methionine.


H. Fang: None. K.P. Stone: None. L. Forney: None. L.C. Sims: None. T.W. Gettys: None.


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