| First Author | Zadjali F | Year | 2012 |
| Journal | FASEB J | Volume | 26 |
| Issue | 8 | Pages | 3282-91 |
| PubMed ID | 22562833 | Mgi Jnum | J:186227 |
| Mgi Id | MGI:5431236 | Doi | 10.1096/fj.12-205583 |
| Citation | Zadjali F, et al. (2012) SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB J 26(8):3282-91 |
| abstractText | Hepatic steatosis is a prominent feature in patients with growth hormone (GH) deficiency. The ubiquitin ligase SOCS2 attenuates hepatic GH signaling by inhibiting the Janus kinase 2 (JAK2)-signal transducer and activator of transcription 5b (STAT5b) axis. Here, we investigated the role of SOCS2 in the development of diet-induced hepatic steatosis and insulin resistance. SOCS2-knockout (SOCS2(-/-)) mice and wild-type littermates were fed for 4 mo with control or high-fat diet, followed by assessment of insulin sensitivity, hepatic lipid content, and expression of inflammatory cytokines. SOCS2(-/-) mice exhibited increased hepatic TG secretion by 77.6% (P<0.001) as compared with wild-type control mice and were protected from high-fat-diet (HFD)-induced hepatic steatosis, showing 49.3% (P<0.01) reduction in liver TG levels compared to HFD-fed wild-type littermates. In contrast, we found that HFD-triggered attenuation of systemic insulin sensitivity was more marked in SOCS2(-/-) mice. Livers from the HFD-fed SOCS2(-/-) mice showed increased NF-kappaB activity as well as elevated expression of genes for the inflammatory cytokines IFN-gamma and IL-6. An inhibitory role of SOCS2 on Toll-like receptor 4 signaling was demonstrated in macrophages obtained from the SOCS2(-/-) and wild-type mice. This study identified SOCS2 as an important regulator of hepatic homeostasis under conditions of high-fat dietary stress.-Zadjali, F., Santana-Farre, R., Vesterlund, M., Carow, B., Mirecki-Garrido, M., Hernandez-Hernandez, I., Flodstrom-Tullberg, M., Parini, P., Rottenberg, M., Norstedt, G., Fernandez-Perez, L., Flores-Morales, A. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. |
