title: Suppressor of cytokine signaling-2 deficiency induces molecular and metabolic changes that partially overlap with growth hormone-dependent effects.
abstract: Suppressor of cytokine signaling-2 (SOCS2)-deficient (SOCS2-/-) mice grow significantly larger than their littermates, suggesting that SOCS2 is important in the negative regulation of the actions of GH and/or IGF-I. The aim of this study was to identify genes and metabolic parameters that might contribute to the SOCS2-/- phenotype. We demonstrate that although SOCS2 deficiency induces significant changes in hepatic gene expression, only a fraction of these overlap with known GH-induced effects in the liver, suggesting that SOCS2 might be an important regulator of other growth factors and cytokines acting on the liver. However, an important role of GH and IGF-I in the phenotype of these animals was demonstrated by an overexpression of IGF-binding protein-3 mRNA in the liver and increased levels of circulating IGF-binding protein-3. Other GH-like effects included diminished serum triglycerides and down-regulation of lipoprotein lipase in adipose tissue. Interestingly, SOCS2-/- mice did not differ from their wild-type littermates in glucose or insulin tolerance tests, which is in contrast with the known diabetogenic effects of GH. Furthermore, there was no evidence of impaired insulin signaling in primary hepatocytes isolated from SOCS2-/- mice. Moreover, increased expression of peroxisome proliferator-activated receptor-gamma coactivator-1alpha mRNA was detected in skeletal muscle, which might contribute to normal glycemic control despite the apparent overactivity of the GH/IGF-I axis. Our data indicate that SOCS2 deficiency partially mimics a state of increased GH activity, but also results in changes that cannot be related to known GH effects.
authors.affiliation: Department of Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rico-Bautista
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Greenhalgh
authors.forename: Petra
authors.initials: P
authors.lastname: Tollet-Egnell
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Hilton
authors.forename: Warren S
authors.initials: WS
authors.lastname: Alexander
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norstedt
authors.forename: Amilcar
authors.initials: A
authors.lastname: Flores-Morales
mesh_terms: D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D016000:Cluster Analysis; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology*; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D050356:Lipid Metabolism; D008071:Lipoprotein Lipase / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D010766:Phosphorylation; D010802:Phylogeny; D012333:RNA, Messenger / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics* / Q000502:physiology*
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007328:Insulin; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D012097:Repressor Proteins; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D008071:Lipoprotein Lipase; D005947:Glucose