Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance

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Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance

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Title: Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance
Author: Al-Share, Qusai Y.; DeAngelis, Anthony M.; Lester, Sumona Ghosh; Bowman, Thomas A.; Ramakrishnan, Sadeesh K.; Abdallah, Simon L.; Russo, Lucia; Patel, Payal R.; Kaw, Meenakshi K.; Raphael, Christian K.; Kim, Andrea Jung; Heinrich, Garrett; Lee, Abraham D.; Kim, Jason K.; Kulkarni, Rohit N.; Philbrick, William M.; Najjar, Sonia M.

Note: Order does not necessarily reflect citation order of authors.

Citation: Al-Share, Q. Y., A. M. DeAngelis, S. G. Lester, T. A. Bowman, S. K. Ramakrishnan, S. L. Abdallah, L. Russo, et al. 2015. “Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance.” Diabetes 64 (8): 2780-2790. doi:10.2337/db14-1772. http://dx.doi.org/10.2337/db14-1772.
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Abstract: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) regulates insulin sensitivity by promoting hepatic insulin clearance. Liver-specific inactivation or global null-mutation of Ceacam1 impairs hepatic insulin extraction to cause chronic hyperinsulinemia, resulting in insulin resistance and visceral obesity. In this study we investigated whether diet-induced insulin resistance implicates changes in hepatic CEACAM1. We report that feeding C57/BL6J mice a high-fat diet reduced hepatic CEACAM1 levels by >50% beginning at 21 days, causing hyperinsulinemia, insulin resistance, and elevation in hepatic triacylglycerol content. Conversely, liver-specific inducible CEACAM1 expression prevented hyperinsulinemia and markedly limited insulin resistance and hepatic lipid accumulation that were induced by prolonged high-fat intake. This was partly mediated by increased hepatic β-fatty acid oxidation and energy expenditure. The data demonstrate that the high-fat diet reduced hepatic CEACAM1 expression and that overexpressing CEACAM1 in liver curtailed diet-induced metabolic abnormalities by protecting hepatic insulin clearance.
Published Version: doi:10.2337/db14-1772
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512217/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:29002539
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