Insulin acutely decreases hepatic fatty acid synthase activity

Cell Metab. 2005 Jul;2(1):43-53. doi: 10.1016/j.cmet.2005.06.001.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Carcinoembryonic Antigen
  • Cell Adhesion Molecules
  • Enzyme Activation
  • Fatty Acid Synthases / metabolism*
  • Female
  • Hepatocytes / cytology
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism
  • Humans
  • Hyperinsulinism / metabolism
  • In Vitro Techniques
  • Insulin / metabolism*
  • Liver / cytology
  • Liver / enzymology*
  • Liver / metabolism
  • Male
  • Mice
  • Mice, Obese
  • Phosphorylation
  • Protein Binding
  • Rats
  • Recombinant Fusion Proteins
  • Tumor Cells, Cultured


  • Antigens, CD
  • CD66 antigens
  • Carcinoembryonic Antigen
  • Ceacam1 protein, mouse
  • Cell Adhesion Molecules
  • Insulin
  • Recombinant Fusion Proteins
  • Fatty Acid Synthases