Abstract 356: Global but not Liver-specific Inactivation of CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 1 Results in Cardiac Hypertrophy and Lipid Accumulation
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<0.05). RWT was not different between LSACC1 and WT (0.59 ± 0.04 vs. 0.64 ± 0.05; n=7/group). Histological sections stained with H&E demonstrated a significant increase in myocyte thickness in Cc1−/− compared to WT(11.0 ± 0.3 μm vs 6.9 ±0.2μm; p<0.001; Figure⇓, 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.