Docosahexanoic acid modifies low-density lipoprotein receptor abundance in HepG2 cells via suppression of the LXRα-Idol pathway.
As a daily supplement, omega‑3 fatty acid is confirmed to be of benefit in hypertriglyceridemia. However, the effect of omega‑3 fatty acids on the low‑density lipoprotein cholesterol (LDL‑C) metabolism remains a controversial issue. In this study, we focused on the regulatory effect of docosahexanoic acid (DHA), one type of omega‑3 fatty acid, exerted on the LDL receptor (LDLR), a determinant regulator of the LDL‑C metabolism, and explored the potential mechanism. We observed that DHA increased hepatic LDLR protein in the presence of 25‑hydroxycholesterol in HepG2 cells but did not alter the mRNA level. Previous studies have identified inducible degrader of the LDLR (Idol) as a novel negative post‑translational modulator of LDLR and a direct transcriptional target of liver X receptor α (LXRα). Since DHA had no effect on the transcriptional level of LDLR, we speculated that the post‑transcriptional pathway LXRα‑Idol participated in this regulation. The results reveal that DHA downregulated the expression of LXRα and Idol in coordination with the upregulation of LDLR expression. Multiple mechanisms are involved in the regulation of LDLR by DHA, and the suppression of the LXRα‑Idol pathway is one of these mechanisms.
Department of Cardiology, Key Laboratory on Assisted Circulation, First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Ying
Y
Zhou
Department of Cardiology, Key Laboratory on Assisted Circulation, First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Yue
Y
Guo
Department of Cardiology, Key Laboratory on Assisted Circulation, First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Xiaodong
X
Zhuang
Department of Cardiology, Key Laboratory on Assisted Circulation, First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
Zhimin
Z
Du
D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D011973:Receptors, LDL; D004281:Docosahexaenoic Acids; C403126:MYLIP protein, human; D044767:Ubiquitin-Protein Ligases