Kaempferol ameliorates symptoms of metabolic syndrome by regulating activities of liver X receptor-β

Minh Hien Hoang, Yaoyao Jia, Boram Mok, Hee jin Jun, Kwang Yeon Hwang, Sung-Joon Lee

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Kaempferol is a dietary flavonol previously shown to regulate cellular lipid and glucose metabolism. However, its molecular mechanisms of action and target proteins have remained elusive, probably due to the involvement of multiple proteins. This study investigated the molecular targets of kaempferol. Ligand binding of kaempferol to liver X receptors (LXRs) was quantified by time-resolved fluorescence resonance energy transfer and surface plasmon resonance analyses. Kaempferol directly binds to and induces the transactivation of LXRs, with stronger specificity for the β-subtype (EC<inf>50</inf>=0.33μM). The oral administration of kaempferol in apolipoprotein-E-deficient mice (150mg/day/kg body weight) significantly reduced plasma glucose and increased high-density lipoprotein cholesterol levels and insulin sensitivity compared with the vehicle-fed control. Kaempferol also reduced plasma triglyceride concentrations and did not cause liver steatosis, a common side effect of potent LXR activation. In immunoblotting analysis, kaempferol reduced the nuclear accumulation of sterol regulatory element-binding protein-1 (SREBP-1). Our results show that the suppression of SREBP-1 activity and the selectivity for LXR-β over LXR-α by kaempferol contribute to the reductions of plasma and hepatic triglyceride concentrations in mice fed kaempferol. They also suggest that kaempferol activates LXR-β and suppresses SREBP-1 to enhance symptoms in metabolic syndrome.

Original languageEnglish
JournalJournal of Nutritional Biochemistry
DOIs
Publication statusAccepted/In press - 2014 Feb 22

Keywords

  • Kaempferol
  • Liver X receptor
  • Metabolic syndrome
  • Peroxisome proliferation-activated receptor
  • Sterol regulatory element-binding protein-1c, Lipid metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

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