Image_3_Stanniocalcin 2 Ameliorates Hepatosteatosis Through Activation of STAT3 Signaling.TIF
Stanniocalcin 2 (STC2), a secreted glycoprotein hormone, regulates many biological processes, including cell proliferation, apoptosis, tumorigenesis, and atherosclerosis. However, its role in hepatic triglyceride metabolism remains unknown. In the present study, we found that expression levels of STC2 were significantly reduced in the livers of leptin-deficient and high fat diet-induced obese mice. Systemic administration of STC2 recombinant protein or adenovirus-mediated overexpression of STC2 markedly attenuated hepatosteatosis and hypertriglyceridemia in obese mice. At the molecular level, we found that STC2 activated the STAT3 signaling pathway to inhibit lipogenic gene expression. Consistently, in vitro studies further showed that inhibition of STAT3 signaling abolished the anti-steatotic effects of STC2. Together, our results revealed an important role of STC2 in the regulation of hepatic triglyceride metabolism, which might provide a potential therapeutic target for the treatment of fatty liver and related metabolic disorders.