Suppressor of cytokine signaling-1a (SOCS1a) is a member of the suppressor of cytokine signaling family, a group of related molecules that mediate the negative regulation of the JAK-STAT pathway. Here, we depleted SOCS1a using the transcription activator-like (TAL) effector nuclease (TALEN) technique to understand its physiological roles in zebrafish. Although elevated levels of JAK-STAT5 activation and erythropoiesis have been observed in socs1a-deficient zebrafish, these animals exhibited normal growth during the early stages. Socs1a-deficient zebrafish began to grow slowly with certain mortalities after 20 days postfertilization (dpf), whereas the heterozygous socs1a-deficient zebrafish exhibited enhanced somatic growth. Decreased adiposity, hepatic steatosis, and insulin resistance were observed in our socs1a-deficient adult zebrafish, which is similar to the lipodystrophy phenotypes observed in mammals. Comparative transcriptomic analyses revealed elevated levels of gluconeogenesis, lipolysis, and hypoxia-inducible response and decreased activities of lipogenesis and glycolysis in the hepatocytes of socs1a-deflicient adult zebrafish. Evident mitochondrial dysfunction has also been observed in hepatocytes from socs1a-deficient zebrafish. Taken together, our results suggest that the negative regulatory roles of SOCS1a on JAK-STAT5 signaling may be involved in the suppression of the erythropoiesis and growth hormone activities, which was also reflected in the enhanced somatic growth performance observed in the heterozygous socs1a-deficient fish. The differences in the effects caused by SOCS1a depletion on insulin sensitivity, lipid metabolism, and inflammatory responses between zebrafish and mammalian models observed here may reflect differences between the functional mechanisms of SOCS members in terrestrial mammals and aquatic teleosts.
Keywords: gene targeting; hepatic steatosis; insulin resistance; suppressor of cytokine signaling-1a; zebrafish.
Copyright © 2015 the American Physiological Society.