Serine signaling governs metabolic homeostasis and health.

Serine has functions that are involved in metabolic homeostasis and health in pathological or stressful situations. Notably, the de novo serine synthesis pathway (SSP) plays a vital role in targeted regulation of immune responses, cell proliferation, and lipid/protein metabolism. The presentation of serine residues derived from SSP may be a signal of stress and provide novel insights into the relationship between metabolic homeostasis and diseases. Here, we summarize the current trends in understanding the regulatory mechanisms of serine metabolism, discuss how serine signaling governs metabolic and antistress processes, including oxidative stress, immunity, energy and lipid metabolism, intestinal microbiota, and the neurological system. We present a possible framework by which serine metabolism maintains metabolic homeostasis and treats human diseases.