Abstract
Neoagarooligosaccharides (NAOS) are produced by β-agarases through the cleavage of β-1,4 linkage in agarose. Here, we investigated the cholesterol-lowering properties of NAOS and its underlying molecular mechanism. Administration of NAOS in mice fed a high-cholesterol diet (HCD) inhibited hepatic fat accumulation and serum LDL cholesterol. Mice fed an HCD showed a decrease in LDL receptor (LDLR) expression, which was reversed by NAOS. Moreover, NAOS enhanced LDLR expression and LDL uptake in hepatocytes. NAOS increased nuclear translocation of SREBP-2, a crucial transcription factor for LDLR gene expression. Increased LDLR luciferase activity, induced by NAOS, was abolished on deletion of SRE in the LDLR promoter. NAOS upregulated LDLR levels via PI3K/Akt-mediated activation of SREBP-2. Furthermore, we demonstrated that NAOS reduced the nuclear HNF-1α, leading to decreased levels of PCSK9, a natural inhibitor of LDLR. These findings indicate that NAOS exhibits hypolipidemic activity, and may serve as a new hypolipidemic drug.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
