Feimin (human) (rec.) (GST)

Feimin, encoded by a gene with a previously unknown function (B230219D22Rik in mice, C5orf24 in humans), is a key modulator of glucose homeostasis. Feimin is a myokine secreted from skeletal muscle during feeding and binds to its receptor, protein tyrosine kinase Mer (MERTK), promoting glucose uptake and inhibiting glucose production by activating AKT. Administration of feimin and insulin synergistically improves blood glucose homeostasis in both normal and diabetic mice. Similar to insulin, feimin suppresses glucose production in the liver and promotes its uptake in adipose tissue and skeletal muscle.

Feimin also works as an intracellular protein as a key activator of adaptive thermogenesis that connects AMP-activated protein kinase (AMPK) signaling to nuclear transcriptional regulation in adipose tissue. Upon cold exposure, AMPK phosphorylates Feimin, promoting translocation of feimin into the nucleus, where it directly interacts with PGC1α to drive thermogenic gene expression. Obesity attenuates feimin phosphorylation and nuclear localization, leading to impaired thermogenic capacity.

Feimin acts as a key negative regulator of high-fat diet (HFD)-induced lipid droplet (LD) accumulation and the microglia-mediated inflammation response, suggesting that it is an attractive therapeutic target for cognitive decline associated with HFDs. Microglial feimin deletion exacerbates lipotoxicity-induced neuroinflammation and cognitive decline.