| First Author | Xu J | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 17845 |
| PubMed ID | 29259301 | Mgi Jnum | J:286897 |
| Mgi Id | MGI:6407509 | Doi | 10.1038/s41598-017-18232-x |
| Citation | Xu J, et al. (2017) Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr (-/-) mice. Sci Rep 7(1):17845 |
| abstractText | Atherosclerotic cardiovascular disease is a leading cause of death in the western world. Increased plasma triglyceride and cholesterol levels are major risk factors for this disease. Carboxylesterase 1 (Ces1/Ces1g) has been shown to play a role in metabolic control. So far, the role of mouse Ces1/Ces1g deficiency in atherosclerosis is not elucidated. We generated Ces1/Ces1g (-/-) mice. Compared to wild-type mice, Ces1/Ces1g (-/-) mice had reduced plasma cholesterol levels. We then generated Ces1g (-/-) Ldlr (-/-) double knockout (DKO) mice, which were fed a Western diet for 16 weeks. Compared to Ldlr (-/-) mice, DKO mice displayed decreased plasma cholesterol and TG levels and reduced atherosclerotic lesions. Interestingly, knockdown of hepatic Ces1/Ces1g in Apoe (-/-) mice resulted in hyperlipidemia and exacerbated Western diet-induced atherogenesis. Mechanistically, global inactivation of Ces1/Ces1g inhibited intestinal cholesterol and fat absorption and Niemann-Pick C1 like 1 expression, and increased macrophage cholesterol efflux by inducing ATP-binding cassette subfamily A member 1 (ABCA1) and ABCG1. Ces1/Ces1g ablation also promoted M2 macrophage polarization and induced hepatic cholesterol 7alpha-hydroxylase and sterol 12alpha-hydroxylase expression. In conclusion, global loss of Ces1/Ces1g protects against the development of atherosclerosis by inhibiting intestinal cholesterol and triglyceride absorption and promoting macrophage cholesterol efflux. |
