Abstract 356: Global but not Liver-specific Inactivation of CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 1 Results in Cardiac Hypertrophy and Lipid Accumulation
Autor: | Eric E Morgan, Kelly J Ledford, Samer Khouri, Anish Purohit, Thomas Bowman, Sonia M Najjar, Sandrine V Pierre |
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Rok vydání: | 2008 |
Předmět: | |
Zdroj: | Circulation. 118 |
ISSN: | 1524-4539 0009-7322 |
DOI: | 10.1161/circ.118.suppl_18.s_289-a |
Popis: | Background: Liver fatty acid synthase (FAS) activity is acutely inhibited by transient increases in insulin via endocytosis of the CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 1 (CEACAM1) and its subsequent binding to FAS. Mice with liver-specific inactivation of Ceacam1 (LSACC1) and mice with null mutation of Ceacam1 (Cc1 −/− ) exhibit hyperinsulinemia, insulin resistance, visceral obesity and increased circulating triglycerides (TG) and free fatty acids (FFA). Hypothesis: Cc1 −/− and LSACC1 hearts exhibit elevated cardiac lipid content and hypertrophy. Results: Using 2D echocardiography, hypertrophy as evidenced by increased relative wall thickness (RWT; [calculated as: (septal wall + posterior wall thickness)/left ventricular end diastolic dimension]) in Cc1 −/− mice compared to wild-type (WT) littermates (0.59 ± 0.06 vs 0.42 ± 0.03; n=14/group; p−/− compared to WT(11.0 ± 0.3 μm vs 6.9 ±0.2μm; p , A), and sections stained with Oil Red O revealed accumulations of neutral lipid in Cc1 −/− hearts (Figure , B). Myocardial triglyceride content and lipoperoxidation were significantly increased in Cc1 −/− hearts compared to WT (Figure , C). Conclusions: Cc1 −/− mice but not LSACC1 mice exhibit myocardial lipid accumulation and hypertrophy. These data suggest that cardiac CEACAM1 plays a key role in regulating cardiac fatty acid metabolism and that cardiac lipid accumulation and hypertrophy in the Cc1−/− mice result, in part, from the loss of cardiac CEACAM1. Figure. Representative photomicrographs (×400) of cardiac tissue from Cc1 +/+ and Cc1 −/− mice demonstrating increased cardiac myocyte thickening (Panel A, H&E staining) and netural lipid accumulation (Panel B oil red O staining. Myocardial triglyceride content and lipid peroxidation as determined by the level of thiobarbituric acid reactive substances (TBARS) were significantly elevated in hearts from Cc1 −/− mice (Panel C). |
Databáze: | OpenAIRE |
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