Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr (-/-) mice.

Title

Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr (-/-) mice.

Creator

Xu Jiesi; Xu Yang; Xu Yanyong; Yin Liya; Zhang Yanqiao

Publisher

Scientific reports

Date

2017
2017-12

Description

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.

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

17845–17845

Issue

1

Volume

7

Citation

Xu Jiesi; Xu Yang; Xu Yanyong; Yin Liya; Zhang Yanqiao, “Global inactivation of carboxylesterase 1 (Ces1/Ces1g) protects against atherosclerosis in Ldlr (-/-) mice.,” NEOMED Bibliography Database, accessed June 20, 2021, https://neomed.omeka.net/items/show/3997.

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