Methionine restriction prevents onset of type 2 diabetes in NZO mice
Methionine restriction prevents onset of type 2 diabetes in NZO mice
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DOI：
10.1096/fj.201900150r
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发表时间：
2019-06-01
期刊：
影响因子：
4.8
通讯作者：
Laeger, Thomas
中科院分区：
文献类型：
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作者：
Castano-Martinez, Teresa;Schumacher, Fabian;Laeger, Thomas
众所周知，饮食蛋氨酸限制（MR）通过增加能量消耗（EE）和胰岛素敏感性来减轻体重。循环成纤维细胞生长因子21（FGF 21）浓度升高已被认为是潜在的潜在机制。我们研究的目的是测试在高脂肪方案的背景下饮食MR是否可以保护小鼠免受2型糖尿病的影响，并研究具有天然低蛋氨酸水平的纯素和素食饮食是否可以调节人类的循环FGF 21。新西兰肥胖（NZO）小鼠，多基因肥胖和2型糖尿病的模型，被放置在等热量的高脂肪饮食（蛋白质，16千卡%，碳水化合物，52千卡%，脂肪，32千卡%），提供蛋氨酸在控制（Con; 0.86%蛋氨酸）或低水平（0.17%）9周。分析葡萄糖稳态和胰岛素敏感性的标志物。在人类中，通过比较纯素饮食和素食饮食与杂食饮食并评估短期素食饮食对FGF 21诱导的影响，研究了低蛋氨酸摄入和循环FGF 21水平。与Con组相比，MR导致NZO小鼠血浆FGF 21水平升高，并防止高血糖症的发生。MR喂养的小鼠表现出胰岛素敏感性增加、血浆脂联素水平升高、EE增加以及皮下白色脂肪组织中产热基因表达上调。食物摄入量和脂肪量没有变化。血浆FGF 21水平明显高于素食者相比，杂食动物和循环中的FGF 21水平增加后4天的素食。这些数据表明，MR诱导FGF 21和保护NZO小鼠免受高脂饮食诱导的葡萄糖耐受不良和2型糖尿病。纯素者和素食者的血糖正常表型可能是由诱导的FGF 21引起的。MR类似于人类的纯素和素食饮食，可能通过增加循环中FGF 21的水平提供代谢益处，值得进一步研究。Castano-Martinez，T.，Schumacher，F.，Schumacher，S.，Kochlik，B.，Weber，D.，Grune，T.，比曼河，McCann，A.，Abraham，K.，Weikert，C.，Kleuser，B.，Schurmann，A.，Laeger，T.在NZO小鼠中，限制蛋氨酸可预防2型糖尿病的发作。
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.