Serine, glutamate, and proline in a high‐fat diet exacerbated metabolite reduction‐induced memory and cognitive decline

Abstract

AbstractEpidemiological studies have shown that excessive consumption of meat may cause memory loss and cognitive decline, but the underlying mechanism is unknown. Here, a high‐chicken‐protein diet but not a high‐pork diet was found to have a markedly negative impact on the enteric nervous system and hippocampal function. Higher serine, glutamate, and proline levels in the high‐chicken‐protein diet inhibited the absorption capacity of amino acids, reduced the levels of neurotransmitters, and further increased hippocampal β‐secretase levels. Alzheimer's disease mouse model and cell studies confirmed that high‐chicken diet‐induced changes in the intestinal function further resulted in metabolic disorders with a reduction in L‐serine and niacinamide in serum, accumulation of hippocampal β‐amyloid, and eventually aggravated memory and cognitive decline. Our findings highlight the importance of serine, glutamate, and proline as systemic mediators of diet–gut–brain axis homeostasis against memory and cognitive dysfunctions associated with excessive intake of chicken.