Insulin acutely decreases hepatic fatty acid synthase activity

Sonia M. Najjar; Yan Yang; Mats A. Fernström; Sang Jun Lee; Anthony M. DeAngelis; George A. Abou Rjaily; Qusai Y. Al-Share; Tong Dai; Tiffany A. Miller; Shobha Ratnam; Randall J. Ruch; Stuart Smith; Sue Hwa Lin; Nicole Beauchemin; Ana Maria Oyarce

doi:10.1016/j.cmet.2005.06.001

Insulin acutely decreases hepatic fatty acid synthase activity

Sonia M. Najjar, Yan Yang, Mats A. Fernström, Sang Jun Lee, Anthony M. DeAngelis, George A. Abou Rjaily, Qusai Y. Al-Share, Tong Dai, Tiffany A. Miller, Shobha Ratnam, Randall J. Ruch, Stuart Smith, Sue Hwa Lin, Nicole Beauchemin, Ana Maria Oyarce

Translational Molecular Pathology

Research output: Contribution to journal › Article › peer-review

78 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	43-53
Number of pages	11
Journal	Cell Metabolism
Volume	2
Issue number	1
DOIs	https://doi.org/10.1016/j.cmet.2005.06.001
State	Published - Jul 2005

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

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10.1016/j.cmet.2005.06.001

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@article{daf2bd96bd4046e989d1e7d7963fa73a,

title = "Insulin acutely decreases hepatic fatty acid synthase activity",

abstract = "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.",

author = "Najjar, {Sonia M.} and Yan Yang and Fernstr{\"o}m, {Mats A.} and Lee, {Sang Jun} and DeAngelis, {Anthony M.} and {Abou Rjaily}, {George A.} and Al-Share, {Qusai Y.} and Tong Dai and Miller, {Tiffany A.} and Shobha Ratnam and Ruch, {Randall J.} and Stuart Smith and Lin, {Sue Hwa} and Nicole Beauchemin and Oyarce, {Ana Maria}",

note = "Funding Information: The authors thank J.A. Smith (University of Pennsylvania) for providing the H35-BT cells, D. Accili (College of Physicians and Surgeons) and W.A. Maltese and D. Giovannucci (Medical University of Ohio) for their critical discussions, and R.A. Hennigar (Emory School of Medicine) and J. Kidwell (Medical University of Ohio) for technical assistance. This work was supported by ADA research award and NIH grants DK 54254 and DK 57497 (to S.M.N.), CA 86342 (to S.-H.L.), and DK 16073 (to S.S.) and by the Canadian Institutes for Health Research MOP-42501 (to N.B.).",

year = "2005",

month = jul,

doi = "10.1016/j.cmet.2005.06.001",

language = "English (US)",

volume = "2",

pages = "43--53",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "1",

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TY - JOUR

T1 - Insulin acutely decreases hepatic fatty acid synthase activity

AU - Najjar, Sonia M.

AU - Yang, Yan

AU - Fernström, Mats A.

AU - Lee, Sang Jun

AU - DeAngelis, Anthony M.

AU - Abou Rjaily, George A.

AU - Al-Share, Qusai Y.

AU - Dai, Tong

AU - Miller, Tiffany A.

AU - Ratnam, Shobha

AU - Ruch, Randall J.

AU - Smith, Stuart

AU - Lin, Sue Hwa

AU - Beauchemin, Nicole

AU - Oyarce, Ana Maria

N1 - Funding Information: The authors thank J.A. Smith (University of Pennsylvania) for providing the H35-BT cells, D. Accili (College of Physicians and Surgeons) and W.A. Maltese and D. Giovannucci (Medical University of Ohio) for their critical discussions, and R.A. Hennigar (Emory School of Medicine) and J. Kidwell (Medical University of Ohio) for technical assistance. This work was supported by ADA research award and NIH grants DK 54254 and DK 57497 (to S.M.N.), CA 86342 (to S.-H.L.), and DK 16073 (to S.S.) and by the Canadian Institutes for Health Research MOP-42501 (to N.B.).

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

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DO - 10.1016/j.cmet.2005.06.001

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AN - SCOPUS:27244458206

SN - 1550-4131

VL - 2

SP - 43

EP - 53

JO - Cell Metabolism

JF - Cell Metabolism

IS - 1

ER -

Insulin acutely decreases hepatic fatty acid synthase activity

Abstract

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