Hexacosanol reduces plasma and hepatic cholesterol by activation of AMP-activated protein kinase and suppression of sterol regulatory element-binding protein-2 in HepG2 and C57BL/6J mice

Ji Hae Lee, Yaoyao Jia, Trung Thanh Thach, Yuri Han, Bobae Kim, Chunyan Wu, Yeonji Kim, Woo Duck Seo, Sung-Joon Lee

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Policosanols have hypocholesterolemic activity; however, the molecular mechanism of the policosanol effects is currently poorly characterized. We hypothesized that hexacosanol, a policosanol compound derived from barley sprout, may decrease cellular and plasma cholesterol levels; we thus investigated the hypocholesterolemic activity and mechanism of hexacosanol on both hepatocytes and high-fat–induced obese C57BL/6J mice. The reduction of total cholesterol, free cholesterol, and cholesteryl ester concentrations was confirmed in hexacosanol-stimulated hepatocytes (−38%, −33%, and −53%, respectively). Plasma, hepatic cholesterol concentrations, and hepatic steatosis were significantly reduced in high-fat–fed mice orally administered with hexacosanol (0.7 mg/kg body weight a day) for 8 weeks compared with those of vehicle-fed control mice (−15% and −40%, respectively). Hexacosanol in fact bound to the allosteric regulation site of AMP-activated protein kinase (AMPK)-β subunit and thus activated AMPK that inhibited the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase by inhibitory phosphorylation. In addition, activation of AMPK by hexacosanol induced hepatic autophagy activity, which could further reduce hepatic lipid accumulation. Alternatively, hexacosanol suppressed the nuclear translocation and activation of sterol regulatory element-binding protein-2 (SREBP-2), a key transcription factor in cholesterol biosynthesis. These results collectively suggest that hexacosanol is a major hypocholesterolemic compound in barley sprouts with regulation of AMPK activation and SREBP-2 suppression. These suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase at both mRNA expression and protein activity levels. In conclusion, hexacosanol activates AMPK and hepatic autophagy and inhibits SREBP2, resulting in hypocholesterolemic activities and improvement of hepatic steatosis.

Original languageEnglish
Pages (from-to)89-99
Number of pages11
JournalNutrition Research
Volume43
DOIs
Publication statusPublished - 2017 Jul 1

Fingerprint

Sterol Regulatory Element Binding Protein 2
policosanol
AMP-Activated Protein Kinases
Inbred C57BL Mouse
Cholesterol
Liver
Cholesterol Esters
Autophagy
Hordeum
Hepatocytes
Oxidoreductases
Allosteric Regulation
Allosteric Site
Obese Mice
Protein Subunits
Transcription Factors
Body Weight
Phosphorylation
Lipids
Messenger RNA

Keywords

  • AMPK
  • Hexacosanol
  • HMG-CoA reductase
  • Hypocholesterolemia
  • SREBP-2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Nutrition and Dietetics

Cite this

Hexacosanol reduces plasma and hepatic cholesterol by activation of AMP-activated protein kinase and suppression of sterol regulatory element-binding protein-2 in HepG2 and C57BL/6J mice. / Lee, Ji Hae; Jia, Yaoyao; Thach, Trung Thanh; Han, Yuri; Kim, Bobae; Wu, Chunyan; Kim, Yeonji; Seo, Woo Duck; Lee, Sung-Joon.

In: Nutrition Research, Vol. 43, 01.07.2017, p. 89-99.

Research output: Contribution to journalArticle

Lee, Ji Hae ; Jia, Yaoyao ; Thach, Trung Thanh ; Han, Yuri ; Kim, Bobae ; Wu, Chunyan ; Kim, Yeonji ; Seo, Woo Duck ; Lee, Sung-Joon. / Hexacosanol reduces plasma and hepatic cholesterol by activation of AMP-activated protein kinase and suppression of sterol regulatory element-binding protein-2 in HepG2 and C57BL/6J mice. In: Nutrition Research. 2017 ; Vol. 43. pp. 89-99.
@article{bb339eac83bf478d9a065f0627d8b94b,
title = "Hexacosanol reduces plasma and hepatic cholesterol by activation of AMP-activated protein kinase and suppression of sterol regulatory element-binding protein-2 in HepG2 and C57BL/6J mice",
abstract = "Policosanols have hypocholesterolemic activity; however, the molecular mechanism of the policosanol effects is currently poorly characterized. We hypothesized that hexacosanol, a policosanol compound derived from barley sprout, may decrease cellular and plasma cholesterol levels; we thus investigated the hypocholesterolemic activity and mechanism of hexacosanol on both hepatocytes and high-fat–induced obese C57BL/6J mice. The reduction of total cholesterol, free cholesterol, and cholesteryl ester concentrations was confirmed in hexacosanol-stimulated hepatocytes (−38{\%}, −33{\%}, and −53{\%}, respectively). Plasma, hepatic cholesterol concentrations, and hepatic steatosis were significantly reduced in high-fat–fed mice orally administered with hexacosanol (0.7 mg/kg body weight a day) for 8 weeks compared with those of vehicle-fed control mice (−15{\%} and −40{\%}, respectively). Hexacosanol in fact bound to the allosteric regulation site of AMP-activated protein kinase (AMPK)-β subunit and thus activated AMPK that inhibited the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase by inhibitory phosphorylation. In addition, activation of AMPK by hexacosanol induced hepatic autophagy activity, which could further reduce hepatic lipid accumulation. Alternatively, hexacosanol suppressed the nuclear translocation and activation of sterol regulatory element-binding protein-2 (SREBP-2), a key transcription factor in cholesterol biosynthesis. These results collectively suggest that hexacosanol is a major hypocholesterolemic compound in barley sprouts with regulation of AMPK activation and SREBP-2 suppression. These suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase at both mRNA expression and protein activity levels. In conclusion, hexacosanol activates AMPK and hepatic autophagy and inhibits SREBP2, resulting in hypocholesterolemic activities and improvement of hepatic steatosis.",
keywords = "AMPK, Hexacosanol, HMG-CoA reductase, Hypocholesterolemia, SREBP-2",
author = "Lee, {Ji Hae} and Yaoyao Jia and Thach, {Trung Thanh} and Yuri Han and Bobae Kim and Chunyan Wu and Yeonji Kim and Seo, {Woo Duck} and Sung-Joon Lee",
year = "2017",
month = "7",
day = "1",
doi = "10.1016/j.nutres.2017.05.013",
language = "English",
volume = "43",
pages = "89--99",
journal = "Nutrition Research",
issn = "0271-5317",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Hexacosanol reduces plasma and hepatic cholesterol by activation of AMP-activated protein kinase and suppression of sterol regulatory element-binding protein-2 in HepG2 and C57BL/6J mice

AU - Lee, Ji Hae

AU - Jia, Yaoyao

AU - Thach, Trung Thanh

AU - Han, Yuri

AU - Kim, Bobae

AU - Wu, Chunyan

AU - Kim, Yeonji

AU - Seo, Woo Duck

AU - Lee, Sung-Joon

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Policosanols have hypocholesterolemic activity; however, the molecular mechanism of the policosanol effects is currently poorly characterized. We hypothesized that hexacosanol, a policosanol compound derived from barley sprout, may decrease cellular and plasma cholesterol levels; we thus investigated the hypocholesterolemic activity and mechanism of hexacosanol on both hepatocytes and high-fat–induced obese C57BL/6J mice. The reduction of total cholesterol, free cholesterol, and cholesteryl ester concentrations was confirmed in hexacosanol-stimulated hepatocytes (−38%, −33%, and −53%, respectively). Plasma, hepatic cholesterol concentrations, and hepatic steatosis were significantly reduced in high-fat–fed mice orally administered with hexacosanol (0.7 mg/kg body weight a day) for 8 weeks compared with those of vehicle-fed control mice (−15% and −40%, respectively). Hexacosanol in fact bound to the allosteric regulation site of AMP-activated protein kinase (AMPK)-β subunit and thus activated AMPK that inhibited the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase by inhibitory phosphorylation. In addition, activation of AMPK by hexacosanol induced hepatic autophagy activity, which could further reduce hepatic lipid accumulation. Alternatively, hexacosanol suppressed the nuclear translocation and activation of sterol regulatory element-binding protein-2 (SREBP-2), a key transcription factor in cholesterol biosynthesis. These results collectively suggest that hexacosanol is a major hypocholesterolemic compound in barley sprouts with regulation of AMPK activation and SREBP-2 suppression. These suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase at both mRNA expression and protein activity levels. In conclusion, hexacosanol activates AMPK and hepatic autophagy and inhibits SREBP2, resulting in hypocholesterolemic activities and improvement of hepatic steatosis.

AB - Policosanols have hypocholesterolemic activity; however, the molecular mechanism of the policosanol effects is currently poorly characterized. We hypothesized that hexacosanol, a policosanol compound derived from barley sprout, may decrease cellular and plasma cholesterol levels; we thus investigated the hypocholesterolemic activity and mechanism of hexacosanol on both hepatocytes and high-fat–induced obese C57BL/6J mice. The reduction of total cholesterol, free cholesterol, and cholesteryl ester concentrations was confirmed in hexacosanol-stimulated hepatocytes (−38%, −33%, and −53%, respectively). Plasma, hepatic cholesterol concentrations, and hepatic steatosis were significantly reduced in high-fat–fed mice orally administered with hexacosanol (0.7 mg/kg body weight a day) for 8 weeks compared with those of vehicle-fed control mice (−15% and −40%, respectively). Hexacosanol in fact bound to the allosteric regulation site of AMP-activated protein kinase (AMPK)-β subunit and thus activated AMPK that inhibited the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase by inhibitory phosphorylation. In addition, activation of AMPK by hexacosanol induced hepatic autophagy activity, which could further reduce hepatic lipid accumulation. Alternatively, hexacosanol suppressed the nuclear translocation and activation of sterol regulatory element-binding protein-2 (SREBP-2), a key transcription factor in cholesterol biosynthesis. These results collectively suggest that hexacosanol is a major hypocholesterolemic compound in barley sprouts with regulation of AMPK activation and SREBP-2 suppression. These suppress 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase at both mRNA expression and protein activity levels. In conclusion, hexacosanol activates AMPK and hepatic autophagy and inhibits SREBP2, resulting in hypocholesterolemic activities and improvement of hepatic steatosis.

KW - AMPK

KW - Hexacosanol

KW - HMG-CoA reductase

KW - Hypocholesterolemia

KW - SREBP-2

UR - http://www.scopus.com/inward/record.url?scp=85021419416&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85021419416&partnerID=8YFLogxK

U2 - 10.1016/j.nutres.2017.05.013

DO - 10.1016/j.nutres.2017.05.013

M3 - Article

C2 - 28676202

AN - SCOPUS:85021419416

VL - 43

SP - 89

EP - 99

JO - Nutrition Research

JF - Nutrition Research

SN - 0271-5317

ER -