Methionine restriction prevents onset of type 2 diabetes in NZO mice

What is it about?

It is well-accepted that energy restriction has a positive effect on metabolic health. The reduction of energy intake improves insulin sensitivity, prevents obesity, and type 2 diabetes. However, dietary protein restriction is emerging as an alternative approach to treat high fat diet-induced obesity and glucose intolerance because it markedly increases plasma fibroblast growth factor 21 (FGF21) concentrations. Similarly, dietary restriction of the essential amino acid methionine is known to mimic metabolic effects of energy and protein restriction with FGF21 as a required mechanism._x000D_ The aim of our study was to test whether a dietary methionine restriction (MR) in the context of obesity and a high-fat diet regimen also protects against type 2 diabetes._x000D_ We demonstrate that a MR prevents the onset of hyperglycemia in obese diabetes-susceptible New Zealand obese mice, presumably via increased plasma adiponectin, independent of food intake and adiposity. The beneficial effects were mediated by FGF21 because in the presence of cystine, MR did not increase FGF21 and did not improve glucose homeostasis. In addition, we observe in humans that circulating FGF21 levels are higher in vegans and vegetarians compared to omnivores, and we demonstrate that FGF21 plasma levels in omnivore humans increase after switching to a vegetarian diet. This is of interest, because lowering the methionine intake for instance with vegan diets, which have naturally low methionine levels, might be linked to health benefits (incl. lower rates of diabetes). In other words, a methionine restrictive diet may be a beneficial nutritional strategy in type 2 diabetes patients.

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