RGD Reference Report - Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse. - Rat Genome Database

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Central role of suppressors of cytokine signaling proteins in hepatic steatosis, insulin resistance, and the metabolic syndrome in the mouse.

Authors: Ueki, K  Kondo, T  Tseng, YH  Kahn, CR 
Citation: Ueki K, etal., Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10422-7. Epub 2004 Jul 6.
RGD ID: 1625677
Pubmed: PMID:15240880   (View Abstract at PubMed)
PMCID: PMC478587   (View Article at PubMed Central)
DOI: DOI:10.1073/pnas.0402511101   (Journal Full-text)

Insulin resistance, obesity, diabetes, dyslipidemia, and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute to the development of these disorders, the molecular mechanism is poorly understood. Here we show that overexpression of suppressors of cytokine signaling (SOCS)-1 and SOCS-3 in liver causes insulin resistance and an increase in the key regulator of fatty acid synthesis in liver, sterol regulatory element-binding protein (SREBP)-1c. Conversely, inhibition of SOCS-1 and -3 in obese diabetic mice improves insulin sensitivity, normalizes the increased expression of SREBP-1c, and dramatically ameliorates hepatic steatosis and hypertriglyceridemia. In obese animals, increased SOCS proteins enhance SREBP-1c expression by antagonizing STAT3-mediated inhibition of SREBP-1c promoter activity. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating insulin signaling and cytokine signaling.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SOCS1HumanHypertriglyceridemia  ISOSocs1 (Mus musculus)associated with ObesityRGD 
SOCS3HumanHypertriglyceridemia  ISOSocs3 (Mus musculus)associated with ObesityRGD 
Socs1RatHypertriglyceridemia  ISOSocs1 (Mus musculus)associated with ObesityRGD 
Socs1MouseHypertriglyceridemia  IMP associated with ObesityRGD 
Socs3RatHypertriglyceridemia  ISOSocs3 (Mus musculus)associated with ObesityRGD 
Socs3MouseHypertriglyceridemia  IMP associated with ObesityRGD 
SOCS1HumanInsulin Resistance  ISOSocs1 (Mus musculus)associated with Diabetes MellitusRGD 
SOCS3HumanInsulin Resistance  ISOSocs3 (Mus musculus)associated with Diabetes MellitusRGD 
Socs1MouseInsulin Resistance  IMP associated with Diabetes MellitusRGD 
Socs1RatInsulin Resistance  ISOSocs1 (Mus musculus)associated with Diabetes MellitusRGD 
Socs3RatInsulin Resistance  ISOSocs3 (Mus musculus)associated with Diabetes MellitusRGD 
Socs3MouseInsulin Resistance  IMP associated with Diabetes MellitusRGD 
SOCS1Humansteatotic liver disease  ISOSocs1 (Mus musculus)associated with ObesityRGD 
SOCS3Humansteatotic liver disease  ISOSocs3 (Mus musculus)associated with ObesityRGD 
Socs1Mousesteatotic liver disease  IMP associated with ObesityRGD 
Socs1Ratsteatotic liver disease  ISOSocs1 (Mus musculus)associated with ObesityRGD 
Socs3Ratsteatotic liver disease  ISOSocs3 (Mus musculus)associated with ObesityRGD 
Socs3Mousesteatotic liver disease  IMP associated with ObesityRGD 

Objects Annotated

Genes (Rattus norvegicus)
Socs1  (suppressor of cytokine signaling 1)
Socs3  (suppressor of cytokine signaling 3)

Genes (Mus musculus)
Socs1  (suppressor of cytokine signaling 1)
Socs3  (suppressor of cytokine signaling 3)

Genes (Homo sapiens)
SOCS1  (suppressor of cytokine signaling 1)
SOCS3  (suppressor of cytokine signaling 3)


Additional Information