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Hypocholesterolemic effect of hexacosanol in HepG2 cells and C57BL/6 mice
Author(s) -
Lee Ji Hae,
Kim Yeojin,
Seo WooDuck,
Lee SungJoon
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1079.10
Subject(s) - ampk , cholesterol , phosphorylation , cholesterol 7 alpha hydroxylase , chemistry , activator (genetics) , stimulation , endocrinology , medicine , hmg coa reductase , reductase , protein kinase a , metabolism , biology , biochemistry , enzyme , gene
AMPK is a cellular energy sensor that orchestrates energy metabolism primarily responding to the cellular AMP levels. The active AMPK has been reported to inhibit HMG‐CoA reductase (HMGCR) by phosphorylation thus reduces cholesterol concentrations. We report that hexacosanol, exhibits AMPK activation assessed with kinase activity assay. The activity was comparable to a known AMPK activator. HepG2 cells stimulated with hexacosanol reduced both cholesterol ester and free cholesterol concentrations by 55% and 34%, respectively. Gene expression analysis revealed that the reduction of cellular cholesterol concentrations was due to activation of AMPK, HMGCR phosphorylation and the reduction of HMGCR expressions. The genes in cholesterol efflux (+190% for CYP7A1) and cholesterol ester synthesis (−39% for ACAT2) were significantly altered in cells with hexacosanol stimulation. The C57BL/6 mice fed hexacosanol for 8 weeks. Plasma cholesterol concentration was reduced in hexacosanol group by 16%. In conclusion, hexacosanol has hypocholesterolemic effect by activating AMPK, HMGCR phosphorylation thus significantly reduces cellular and plasma cholesterol concentrations in both of hepatocytes and mice.