Abstract
BackgroundApolipoprotein M (apoM), as a novel apolipoprotein which is mainly expressed in liver and kidney tissues, is associated with development and progression of atherosclerosis and diabetes. Our group have recently shown that Dihydrocapsaicin(DHC)can significantly decrease atherosclerotic plaque formation in apoE−/− mice. However, the effect and possible mechanism of DHC on apoM expression remain unclear.MethodsHepG2 cells were treated with 0 μM, 25 μM, 50 μM and 100 μM DHC for 24 h or were treated with 100 μM DHC for 0, 6, 12, and 24 h, respectively. The mRNA levels and protein levels were measured by real-time quantitative PCR and western blot analysis, respectively.ResultsWe found that DHC markedly decreased expression of apoM at both mRNA and protein level in HepG2 cells in a dose-dependent and time-dependent manner. Expression of Foxa2 was decreased while expression of LXRα was increased by DHC treatment in HepG2 cells. In addittion, overexpression of Foxa2 markedly compensated the inhibition effect induced by DHC on apoM expression. LXRα small interfering RNA significantly abolished the inhibition effect which induced by DHC on apoM expression. The liver of C57BL/6 mice treated with DHC had significantly lower expression of apoM. Furthermore, the liver had lower expression of Foxa2 while had higher expression of LXRα.ConclusionsDHC could down-regulate apoM expression through inhibiting Foxa2 expression and enhancing LXRα expression in HepG2 cells.
Highlights
Capsaicinoids, including capsaicin and dihydrocapsaicin (DHC), which together typically represent 85–90% of the total capsaicinoid content in ‘hot chilli peppers’ extract, and its minor components include nordihydrocapsaicin, homocapsaicin and homodihydrocapsaicin [1,2]
We demonstrated that DHC could markedly down-regulate Apolipoprotein M (apoM) expression through inhibiting Foxa2 expression and enhancing Liver X Receptor α (LXRα) expression in HepG2 cells
Foxa2 is involved in DHC-induced down-regulation of apoM in HepG2 cells Previously researches revealed that apoM expression is directly regulated by Foxa2, which is a transcription factor involved in hepatic development via the regulation of glucose homeostasis in liver
Summary
Capsaicinoids, including capsaicin and dihydrocapsaicin (DHC), which together typically represent 85–90% of the total capsaicinoid content in ‘hot chilli peppers’ extract, and its minor components include nordihydrocapsaicin, homocapsaicin and homodihydrocapsaicin [1,2] These spice principles have been proved to augment carbohydrate metabolism [3,4], energy expenditure [5] and lipid metabolism [6,7,8] in rodents and/or humans, and have been successfully used in the treatment of high-fat/high-cholesterol die [1]. Futhermore, Serum apoM concentrations and hepatic APOM mRNA levels were significantly reduced in the hyperglycemic rats, indicating that the low expression levels of apoM in these diabetic animals could be ascribed to hyperglycemia [20] These observations support the notion that apoM is linked to cholesterol metabolism and diabetes. The effect and possible mechanism of DHC on apoM expression remain unclear
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
