Kaempferol reduces hepatic triglyceride accumulation by inhibiting Akt

Minh Hien Hoang, Yaoyao Jia, Ji Hae Lee, Yeonji Kim, Sung-Joon Lee

Research output: Contribution to journalArticle

Abstract

In this paper, we studied the mechanism of the triglyceride (TG)-lowering effect of kaempferol in vitro and in vivo. Kaempferol showed LXR agonistic activities without inducing TGs or the expression of several lipogenic genes in cultured cells. A luciferase and qPCR analysis showed that kaempferol increased the transactivation of PPARα and PPARδ and stimulated gene expression associated with fatty acid oxidation and uptake in hepatocytes. More importantly, kaempferol inhibited protein kinase B (Akt) activity and suppressed SREBP-1 activation via multiple mechanisms, including through increasing Insig-2a expression, reducing SREBP-1 phosphorylation, and increasing GSK-3 phosphorylation. Collectively, these actions inhibited the SREBP-1 activation process. Furthermore, as an Akt/mTOR pathway inhibitor, kaempferol led to the induction of hepatic autophagy and resulted in a decrease in lipid droplet formation in the mouse liver. These findings demonstrate that kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Practical applications: Kaempferol is a major dietary flavonoid in various plant-based foods, and it is used as a valuable ingredient in functional foods, with numerous beneficial properties such as anticancer, antioxidant, and anti-atherosclerotic activities. Kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Currently, the number of people with hyperlipidemia is rapidly growing in both developed and developing societies; thus, we propose that kaempferol could be used for therapeutic interventions aimed at the treatment of these individuals.

Original languageEnglish
Article numbere13034
JournalJournal of Food Biochemistry
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

kaempferol
Peroxisome Proliferator-Activated Receptors
Triglycerides
triacylglycerols
liver
Liver
phosphorylation
Phosphorylation
Glycogen Synthase Kinase 3
plant-based foods
Proto-Oncogene Proteins c-akt
Edible Plants
Functional Food
beta oxidation
autophagy
Autophagy
hyperlipidemia
transcriptional activation
luciferase
Hyperlipidemias

Keywords

  • AKT
  • autophagy
  • kaempferol
  • PPARs
  • triglycerides

ASJC Scopus subject areas

  • Biophysics
  • Food Science
  • Pharmacology
  • Cell Biology

Cite this

Kaempferol reduces hepatic triglyceride accumulation by inhibiting Akt. / Hoang, Minh Hien; Jia, Yaoyao; Lee, Ji Hae; Kim, Yeonji; Lee, Sung-Joon.

In: Journal of Food Biochemistry, 01.01.2019.

Research output: Contribution to journalArticle

@article{f5fbd69bfb8348d188374fa2cf2ec11c,
title = "Kaempferol reduces hepatic triglyceride accumulation by inhibiting Akt",
abstract = "In this paper, we studied the mechanism of the triglyceride (TG)-lowering effect of kaempferol in vitro and in vivo. Kaempferol showed LXR agonistic activities without inducing TGs or the expression of several lipogenic genes in cultured cells. A luciferase and qPCR analysis showed that kaempferol increased the transactivation of PPARα and PPARδ and stimulated gene expression associated with fatty acid oxidation and uptake in hepatocytes. More importantly, kaempferol inhibited protein kinase B (Akt) activity and suppressed SREBP-1 activation via multiple mechanisms, including through increasing Insig-2a expression, reducing SREBP-1 phosphorylation, and increasing GSK-3 phosphorylation. Collectively, these actions inhibited the SREBP-1 activation process. Furthermore, as an Akt/mTOR pathway inhibitor, kaempferol led to the induction of hepatic autophagy and resulted in a decrease in lipid droplet formation in the mouse liver. These findings demonstrate that kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Practical applications: Kaempferol is a major dietary flavonoid in various plant-based foods, and it is used as a valuable ingredient in functional foods, with numerous beneficial properties such as anticancer, antioxidant, and anti-atherosclerotic activities. Kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Currently, the number of people with hyperlipidemia is rapidly growing in both developed and developing societies; thus, we propose that kaempferol could be used for therapeutic interventions aimed at the treatment of these individuals.",
keywords = "AKT, autophagy, kaempferol, PPARs, triglycerides",
author = "Hoang, {Minh Hien} and Yaoyao Jia and Lee, {Ji Hae} and Yeonji Kim and Sung-Joon Lee",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/jfbc.13034",
language = "English",
journal = "Journal of Food Biochemistry",
issn = "0145-8884",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Kaempferol reduces hepatic triglyceride accumulation by inhibiting Akt

AU - Hoang, Minh Hien

AU - Jia, Yaoyao

AU - Lee, Ji Hae

AU - Kim, Yeonji

AU - Lee, Sung-Joon

PY - 2019/1/1

Y1 - 2019/1/1

N2 - In this paper, we studied the mechanism of the triglyceride (TG)-lowering effect of kaempferol in vitro and in vivo. Kaempferol showed LXR agonistic activities without inducing TGs or the expression of several lipogenic genes in cultured cells. A luciferase and qPCR analysis showed that kaempferol increased the transactivation of PPARα and PPARδ and stimulated gene expression associated with fatty acid oxidation and uptake in hepatocytes. More importantly, kaempferol inhibited protein kinase B (Akt) activity and suppressed SREBP-1 activation via multiple mechanisms, including through increasing Insig-2a expression, reducing SREBP-1 phosphorylation, and increasing GSK-3 phosphorylation. Collectively, these actions inhibited the SREBP-1 activation process. Furthermore, as an Akt/mTOR pathway inhibitor, kaempferol led to the induction of hepatic autophagy and resulted in a decrease in lipid droplet formation in the mouse liver. These findings demonstrate that kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Practical applications: Kaempferol is a major dietary flavonoid in various plant-based foods, and it is used as a valuable ingredient in functional foods, with numerous beneficial properties such as anticancer, antioxidant, and anti-atherosclerotic activities. Kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Currently, the number of people with hyperlipidemia is rapidly growing in both developed and developing societies; thus, we propose that kaempferol could be used for therapeutic interventions aimed at the treatment of these individuals.

AB - In this paper, we studied the mechanism of the triglyceride (TG)-lowering effect of kaempferol in vitro and in vivo. Kaempferol showed LXR agonistic activities without inducing TGs or the expression of several lipogenic genes in cultured cells. A luciferase and qPCR analysis showed that kaempferol increased the transactivation of PPARα and PPARδ and stimulated gene expression associated with fatty acid oxidation and uptake in hepatocytes. More importantly, kaempferol inhibited protein kinase B (Akt) activity and suppressed SREBP-1 activation via multiple mechanisms, including through increasing Insig-2a expression, reducing SREBP-1 phosphorylation, and increasing GSK-3 phosphorylation. Collectively, these actions inhibited the SREBP-1 activation process. Furthermore, as an Akt/mTOR pathway inhibitor, kaempferol led to the induction of hepatic autophagy and resulted in a decrease in lipid droplet formation in the mouse liver. These findings demonstrate that kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Practical applications: Kaempferol is a major dietary flavonoid in various plant-based foods, and it is used as a valuable ingredient in functional foods, with numerous beneficial properties such as anticancer, antioxidant, and anti-atherosclerotic activities. Kaempferol exerts its TG-lowering effect via Akt inhibition and activation of PPARα and PPARδ. Currently, the number of people with hyperlipidemia is rapidly growing in both developed and developing societies; thus, we propose that kaempferol could be used for therapeutic interventions aimed at the treatment of these individuals.

KW - AKT

KW - autophagy

KW - kaempferol

KW - PPARs

KW - triglycerides

UR - http://www.scopus.com/inward/record.url?scp=85071860729&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85071860729&partnerID=8YFLogxK

U2 - 10.1111/jfbc.13034

DO - 10.1111/jfbc.13034

M3 - Article

JO - Journal of Food Biochemistry

JF - Journal of Food Biochemistry

SN - 0145-8884

M1 - e13034

ER -