Dietary GABA and its combination with vigabatrin mimic calorie restriction and induce antiobesity-like effects in lean mice

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.