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

Research output: Contribution to journalArticle

32 Citations (Scopus)

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-/- 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
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 2012

Fingerprint

High Fat Diet
Nutrition
Growth Hormone
Insulin Resistance
Fats
STAT5 Transcription Factor
Janus Kinase 2
Insulin
Cytokines
Toll-Like Receptor 4
Macrophages
Dietary Fats
Liver
Ligases
Ubiquitin
Interleukin-6
Genes
Lipids
Knockout Mice
Homeostasis

Keywords

  • Growth hormone
  • Inflammation
  • Suppressor of cytokine signaling

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Zadjali, F., Santana-Farre, R., Vesterlund, M., Carow, B., Mirecki-Garrido, M., Hernandez-Hernandez, I., ... Flores-Morales, A. (2012). SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB Journal, 26(8), 3282-3291. https://doi.org/10.1096/fj.12-205583

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

In: FASEB Journal, Vol. 26, No. 8, 08.2012, p. 3282-3291.

Research output: Contribution to journalArticle

Zadjali, F, Santana-Farre, R, Vesterlund, M, Carow, B, Mirecki-Garrido, M, Hernandez-Hernandez, I, Flodström-Tullberg, M, Parini, P, Rottenberg, M, Norstedt, G, Fernandez-Perez, L & Flores-Morales, A 2012, 'SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice', FASEB Journal, vol. 26, no. 8, pp. 3282-3291. https://doi.org/10.1096/fj.12-205583
Zadjali F, Santana-Farre R, Vesterlund M, Carow B, Mirecki-Garrido M, Hernandez-Hernandez I et al. SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. FASEB Journal. 2012 Aug;26(8):3282-3291. https://doi.org/10.1096/fj.12-205583
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. / SOCS2 deletion protects against hepatic steatosis but worsens insulin resistance in high-fat-diet-fed mice. In: FASEB Journal. 2012 ; Vol. 26, No. 8. pp. 3282-3291.
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