TY  - JOUR
A1  - Castaño Martínez, María Teresa
A1  - Schumacher, Fabian
A1  - Schumacher, Silke
A1  - Kochlik, Bastian
A1  - Weber, Daniela
A1  - Grune, Tilman
A1  - Biemann, Ronald
A1  - McCann, Adrian
A1  - Abraham, Klaus
A1  - Weikert, Cornelia
A1  - Kleuse, Burkhard
A1  - Schürmann, Annette
A1  - Laeger, Thomas
T1  - Methionine restriction prevents onset of type 2 diabetes in NZO mice
JF  - The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology
N2  - Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet-induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.-Castano-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schurmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.
KW  - energy expenditure
KW  - hyperglycemia
KW  - obesity
KW  - vegan
KW  - vegetarian
Y1  - 2019
U6  - https://doi.org/10.1096/fj.201900150R
SN  - 0892-6638
SN  - 1530-6860
VL  - 33
IS  - 6
SP  - 7092
EP  - 7102
PB  - Federation of American Societies for Experimental Biology
CY  - Bethesda
ER  -