Lycopene amends LPS induced oxidative stress and hypertriglyceridemia via modulating PCSK-9 expression and Apo-CIII mediated lipoprotein lipase activity

This study was undertaken to uncover the regulatory role of lycopene in targeting lipopolysaccharide (LPS) induced oxidative stress and inflammatory cascades and subsequent regulation of proprotein convertase subtilisin/kexin type-9 (PCSK-9) expression via sterol regulatory element binding protein-2 (SREBP-2) and hepatocyte nuclear factor-1 alpha (HNF-1 alpha). Further, protein-protein interaction (PPI) studies for Lycopene-Apo-CIII complex against lipoprotein lipase (LPL) were also performed to assess its regulatory role behind the enhanced circulatory TG/TRLs clearance. Lycopene treatment down-regulated hepatocyte PCSK-9 expression via down-regulation of HNF-1 alpha, whereas, LDL-receptor (LDL-R) was up-regulated by subsequent up-regulation of SREBP2. PPI studies showed that lycopene diminishes the affinity of Apo-CIII to complex with LPL (Delta G: -917.1 Kcal/mol) resulting in increased LPL functionality and TRLs clearance. Moreover, lycopene also ameliorated LPS stimulated oxidative-stress via enhanced total antioxidant and HDL associated PON-1 activity in addition to down-regulate the expression and plasma level of inflammatory mediators. Based on above findings, we concluded that lycopene exhibits dual role in targeting LPS induced oxidative stress and hypertriglyceridemia via down-regulation of PCSK-9, making greater no. of surface LDL-R available for LPS processing and clearance, as well as increased LPL activity through inhibition of Apo-CIII.