Low-Carbohydrate and High-Protein Diet Suppresses Working Memory Function in Healthy Mice

Low-carbohydrate and high-protein (LC-HP) diets are acceptable for improving physiological and metabolic parameters. However, the effects of LC-HP diets on the brain are unclear, which depend on glycometabolism for neuronal activity. Since astrocyte-neuron lactate shuttle (ANLS) is an essential pathway for maintaining brain functions, we investigated the changes in hippocampal memory function. In addition, the alteration of lactate transporter constituting ANLS and ANLS-related neurotrophic factors by feeding LC-HP diets was evaluated in healthy mice. C57BL/6 mice were divided into two groups: a group feeding LC-HP diet (24.6% carbohydrate, 57.6% protein, and 17.8% fat as percentages of calories) and a group feeding control diet (58.6% carbohydrate, 24.2% protein, and 17.2% fat as percentages of calories). Here, we found that 4 wk of LC-HP diet feeding suppressed memory function in mice evaluated by Y-maze. Hippocampal mRNA levels of lactate transporters, such as Mct1, Mct4, and Mct2, were unchanged with feeding LC-HP diets; however, LC-HP diets significantly decreased Dcx and Igf-1 receptor mRNA levels in the hippocampus. Bdnf and its related signaling in mice hippocampus exhibited no change by LC-HP diets. Although there was non-influence in the lactate-transport system, LC-HP diets would suppress hippocampal working memory with dysregulation of neuroplasticity. The current data propose the importance of food choices for maintaining hippocampal health.