RGD Reference Report - Insulin acutely decreases hepatic fatty acid synthase activity. - Rat Genome Database

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Insulin acutely decreases hepatic fatty acid synthase activity.

Authors: Najjar, SM  Yang, Y  Fernstrom, MA  Lee, SJ  Deangelis, AM  Rjaily, GA  Al-Share, QY  Dai, T  Miller, TA  Ratnam, S  Ruch, RJ  Smith, S  Lin, SH  Beauchemin, N  Oyarce, AM 
Citation: Najjar SM, etal., Cell Metab. 2005 Jul;2(1):43-53.
RGD ID: 11059593
Pubmed: PMID:16054098   (View Abstract at PubMed)
DOI: DOI:10.1016/j.cmet.2005.06.001   (Journal Full-text)

Insulin is viewed as a positive regulator of fatty acid synthesis by increasing fatty acid synthase (FAS) mRNA transcription. We uncover a new mechanism by which insulin acutely reduces hepatic FAS activity by inducing phosphorylation of the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and its interaction with FAS. Ceacam1 null mice (Cc1(-/-)) show loss of insulin's ability to acutely decrease hepatic FAS activity. Moreover, adenoviral delivery of wild-type, but not the phosphorylation-defective Ceacam1 mutant, restores the acute effect of insulin on FAS activity in Cc1(-/-) primary hepatocytes. Failure of insulin to acutely reduce hepatic FAS activity in hyperinsulinemic mice, including L-SACC1 transgenics with liver inactivation of CEACAM1, and Ob/Ob obese mice, suggests that the acute effect of insulin on FAS activity depends on the prior insulinemic state. We propose that this mechanism acts to reduce hepatic lipogenesis incurred by insulin pulses during refeeding.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ceacam1Ratnegative regulation of fatty acid biosynthetic process involved_inIMP PMID:16054098UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FasnRatcytoplasm located_inIDA PMID:16054098UniProt 
Ceacam1Ratplasma membrane located_inIDA PMID:16054098UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Ceacam1Ratprotein binding enablesIPIUniProtKB:P12785PMID:16054098UniProt 
FasnRatprotein binding enablesIPIUniProtKB:P16573PMID:16054098UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Ceacam1  (CEA cell adhesion molecule 1)
Fasn  (fatty acid synthase)


Additional Information