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Title: | SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice | Authors: | Zadjali, Fahad Santana-Farre, Ruyman Vesterlund, Mattias Carow, Berit Mirecki-Garrido, Mercedes Hernandez-Hernandez, Irene Flodström-Tullberg, Malin Parini, Paolo Rottenberg, Martin Norstedt, Gunnar Fernandez-Perez, Leandro Flores-Morales, Amilcar |
UNESCO Clasification: | 32 Ciencias médicas 2302 Bioquímica |
Keywords: | Lacking Suppressor Liver Deficiency Obesity Steatohepatitis, et al |
Issue Date: | 2012 | Project: | Estudio Funcional y Molecular de Las Proteínas Socs en Un Modelo de Resistencia Hepática A Insulina. | Journal: | FASEB Journal | Abstract: | 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-kappa B 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. | URI: | https://accedacris.ulpgc.es/handle/10553/48250 | ISSN: | 0892-6638 | DOI: | 10.1096/fj.12-205583 | Source: | Faseb Journal[ISSN 0892-6638],v. 26 (8), p. 3282-3291 |
Appears in Collections: | Artículos |
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