Abstract
Dietary protein restriction and dietary methionine restriction (MR) produce a comparable series of behavioral, physiological, biochemical, and transcriptional responses. Both dietary regimens produce a similar reduction in intake of sulfur amino acids (e.g., methionine and cystine), and both diets increase expression and release of hepatic FGF21. Given that FGF21 is an essential mediator of the metabolic phenotype produced by both diets, an important unresolved question is whether dietary protein restriction represents de facto methionine restriction. Using diets formulated from either casein or soy protein with matched reductions in sulfur amino acids, we compared the ability of the respective diets to recapitulate the metabolic phenotype produced by methionine restriction using elemental diets. Although the soy-based control diets supported faster growth compared to casein-based control diets, casein-based protein restriction and soy-based protein restriction produced comparable reductions in body weight and fat deposition, and similar increases in energy intake, energy expenditure, and water intake. In addition, the prototypical effects of dietary MR on hepatic and adipose tissue target genes were similarly regulated by casein- and soy-based protein restriction. The present findings support the feasibility of using restricted intake of diets from various protein sources to produce therapeutically effective implementation of dietary methionine restriction.
Highlights
Studies of the short-term metabolic effects of dietary protein restriction and methionine restriction (MR) have been pursued in parallel in recent years, with studies conducted in the last decade identifying significant similarities among the responses to the two dietary regimens
Using mice fed protein-restricted diets formulated with different protein sources but with matched restrictions of sulfur amino acids, it is shown that casein protein restriction and soy protein restriction produce comparable metabolic effects on energy balance, hepatic gene expression, and adipose tissue gene expression that are consistent with the biological responses to dietary MR
Casein was restricted from 20% to 5% and soy was restricted from 20% to 10% to produce a comparable degree of sulfur amino acid (e.g., SAA) restriction
Summary
Studies of the short-term metabolic effects of dietary protein restriction and methionine restriction (MR) have been pursued in parallel in recent years, with studies conducted in the last decade identifying significant similarities among the responses to the two dietary regimens (reviewed in [1,2,3,4,5]). An even less severe restriction involving a 2- to 3-fold reduction in dietary methionine was without effect on growth, energy balance, or body composition [8] These studies illustrate that restricting dietary methionine to a specific range is highly beneficial, while a more severe restriction can be detrimental, and a less severe restriction is without effect [8]. Using mice fed protein-restricted diets formulated with different protein sources but with matched restrictions of sulfur amino acids, it is shown that casein protein restriction and soy protein restriction produce comparable metabolic effects on energy balance, hepatic gene expression, and adipose tissue gene expression that are consistent with the biological responses to dietary MR
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