Dietary GABA and its combination with vigabatrin mimic calorie restriction and induce antiobesity-like effects in lean mice
Dietary GABA and its combination with vigabatrin mimic calorie restriction and induce antiobesity-like effects in lean mice
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DOI：
10.1016/j.jff.2021.104367
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发表时间：
2021-03
影响因子：
5.6
通讯作者：
Kanako Sato;Takumi Komaru;Takeshi Arima;Chanakarn Jardson;N. Yanaka;Thanutchaporn Kumrungsee
中科院分区：
文献类型：
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作者：
Kanako Sato;Takumi Komaru;Takeshi Arima;Chanakarn Jardson;N. Yanaka;Thanutchaporn Kumrungsee
γ-氨基丁酸（GABA）的抗肥胖和抗糖尿病作用主要通过调节小鼠血糖和胰岛素来实现。目前尚不清楚饮食中的GABA是否通过其他途径发挥抗肥胖作用。在此，我们报告说，高饮食GABA摄入量（5%）显着抑制食物摄入量（-30%），体重增加，脂肪积累，诱导酮生成，改善葡萄糖代谢，并提高循环GABA和β-氨基异丁酸的水平。这些变化表明，5%的GABA摄入量可能会导致热量限制。有趣的是，低剂量饮食GABA（0.5%和2%）和氨己烯酸（GABA转氨酶（GABA-T）的抑制剂）的组合显着增加循环GABA的水平，并强烈发挥抗肥胖样作用。脑GABA水平在摄入5% GABA后略有增加，但在摄入低剂量GABA-氨己烯酸组合后显著增加。因此，通过靶向GABA-T来操纵外周和大脑GABA代谢可能会导致开发用于暴饮暴食和肥胖的新干预措施。
The anti-obesity and anti-diabetic effects of γ-aminobutyric acid (GABA) are mainly expressed via glucose and insulin regulation in mice. It is unknown whether dietary GABA exerts anti-obesity effects via other pathways. Herein, we report that a high dietary GABA intake (5%) significantly suppressed food intake (−30%), body-weight gain, and fat accumulation, induced ketogenesis, improved glucose metabolism, and elevated the levels of circulating GABA and β-aminoisobutyric acid. These changes suggest that 5% GABA intake possibly induces calorie restriction. Interestingly, a combination of low-dose dietary GABA (0.5% and 2%) and vigabatrin (inhibitor of GABA transaminase (GABA-T)) markedly increased the levels of circulating GABA and strongly exerted antiobesity-like effects. Brain GABA levels increased slightly upon 5% GABA intake, but significantly upon intake of the low-dose GABA–vigabatrin combination. Therefore, the manipulation of peripheral and brain GABA metabolism by targeting GABA-T may lead to the development of novel interventions for overeating and obesity.