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- Title
Forced Hepatic Overexpression of CEACAM1 Curtails Diet-Induced Insulin Resistance.
- Authors
Al-Share, Qusai Y.; DeAngelis, Anthony M.; Ghosh Lester, Sumona; Bowman, Thomas A.; Ramakrishnan, Sadeesh K.; Abdallah, Simon L.; Russo, Lucia; Patel, Payal R.; Kaw, Meenakshi K.; Raphael, Christian K.; Jung Kim, Andrea; Heinrich, Garrett; Lee, Abraham D.; Kim, Jason K.; Kulkarni, Rohit N.; Philbrick, William M.; Najjar, Sonia M.
- 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.
- Subjects
INSULIN resistance; OBESITY; CARCINOEMBRYONIC antigen; CELL adhesion molecules; HEPATIC manifestations of general diseases
- Publication
Diabetes, 2015, Vol 64, Issue 8, p2780
- ISSN
0012-1797
- Publication type
Article
- DOI
10.2337/db14-1772