SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice

Fahad Zadjali, Ruyman Santana-Farre, Mattias Vesterlund, Berit Carow, Mercedes Mirecki-Garrido, Irene Hernandez-Hernandez, Malin Flodström-Tullberg, Paolo Parini, Martin Rottenberg, Gunnar Norstedt, Leandro Fernandez-Perez, Amilcar Flores-Morales*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

55 Citations (Scopus)


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-κB activity as well as elevated expression of genes for the inflammatory cytokines IFN-γ 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.

Original languageEnglish
Pages (from-to)3282-3291
Number of pages10
JournalFASEB Journal
Issue number8
Publication statusPublished - Aug 2012


  • Growth hormone
  • Inflammation
  • Suppressor of cytokine signaling

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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