IMR Press / FBL / Volume 29 / Issue 4 / DOI: 10.31083/j.fbl2904131
Open Access Original Research
Targeted Knockdown of Hepatic Δ-5 Fatty Acid Desaturase FADS1 Aggravates Atherosclerosis in ApoE-/- Mice
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1 Department of Vascular Surgery, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China
2 Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, 100029 Beijing, China
*Correspondence: (Sheng Wang)
Front. Biosci. (Landmark Ed) 2024, 29(4), 131;
Submitted: 24 September 2023 | Revised: 15 February 2024 | Accepted: 6 March 2024 | Published: 29 March 2024
Copyright: © 2024 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: The endogenous metabolism of polyunsaturated fatty acids is regulated by the fatty acid desaturase (FADS) gene cluster and is strongly associated with diseases such as atherosclerosis, dyslipidemia, and type 2 diabetes. However, the association between FADS and atherosclerosis remains a subject of debate. Methods: In this study, we specifically investigated the physiological role of Δ-5 fatty acid desaturase (FADS1) in aortic and peripheral vessel (namely, the femoral artery) atherosclerosis by targeting the selective knockdown of hepatic Fads1 in apolipoprotein E-null (ApoE-/-) mice with antisense oligonucleotides (ASOs). Results: Knockdown of hepatic Fads1 in ApoE-/- mice exacerbated aortic atherosclerosis and non-alcoholic fatty liver disease (NAFLD), resulting in weight loss. Upregulation of FADS1 mRNA expression in more severe atherosclerosis vascular tissues potentially caused the upregulation of angiopoietin-like 4 expression. Conclusions: Our study demonstrated that knockdown of hepatic Fads1 in ApoE-/- mice aggravates spontaneous atherosclerosis and NAFLD but does not affect peripheral atherosclerosis (femoral artery) induced by vascular cuff combined with tandem stenosis.

Δ-5 fatty acid desaturase
antisense oligonucleotides
angiopoietin-like 4
2022409422/Director’s Fund of Beijing Anzhen Hospital
Fig. 1.
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