SHLP2 is one of six small humanin-like peptides (SHLP1 to 6) encoded by the 16S rRNA gene of the mitochondrial DNA genome, which is implicated in several biological processes such as aging and oxidative stress. SHLP2 induces beta-Arrestin recruitment to CXCR7 with an EC50 of 0.9696µM, and also binds directly to CXCR7, causing its internalization without affecting CXCR4. In vivo, administration of SHLP2 results in the suppression of food intake, activation of thermogenesis, and prevention of diet-induced obesity in mice. Activation of pro-opiomelanocortin (POMC) neurons by SHLP2 in the arcuate nucleus of the hypothalamus is involved in these processes. SHLP2 can also improve glucose tolerance and insulin sensitivity in vivo.
