Targeted Knockdown of Hepatic Δ-5 Fatty Acid Desaturase FADS1 Aggravates Atherosclerosis in ApoE-/- Mice

• Published in: Frontiers in bioscience (Landmark. Print) Vol. 29; no. 4; p. 131
• Main Authors: Liu, Qiulei, Wang, Peng, Yang, Zhao, Dai, Yue, Wang, Sheng
• Format: Journal Article
• Language: English
• Published: Singapore IMR Press 29.03.2024
• Subjects: angiopoietin-like 4; Animals; antisense oligonucleotides; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; atherosclerosis; Atherosclerosis - genetics; Atherosclerosis - metabolism; Delta-5 Fatty Acid Desaturase - metabolism; Fatty Acid Desaturases - genetics; Fatty Acid Desaturases - metabolism; Gene Knockdown Techniques; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Non-alcoholic Fatty Liver Disease - genetics; Non-alcoholic Fatty Liver Disease - metabolism; Oligonucleotides, Antisense - genetics; δ-5 fatty acid desaturase; atherosclerosis; Δ-5 fatty acid desaturase; angiopoietin-like 4; antisense oligonucleotides
• ISSN: 2768-6701; 2768-6698; 2768-6698
• DOI: 10.31083/j.fbl2904131

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.