Therapeutic potential of panduratin A, LKB1-dependent AMP-activated protein kinase stimulator, with activation of PPARα/δ for the treatment of obesity

D. Kim, M. S. Lee, K. Jo, K. E. Lee, J. K. Hwang

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Aim: AMP-activated protein kinase (AMPK) activators have shown potential as therapeutic agents for metabolic disorders. This study was conducted to evaluate therapeutic potential of panduratin (PAN) A, a natural AMPK stimulator, with activation of PPARα/δ for the treatment of obesity. Methods: We used the novel AMPK activator PAN A, a natural compound isolated from Boesenbergia pandurata rhizomes, to investigate the regulation of LKB1-dependent AMPK-PPARα/δ signalling by western blot, reporter gene assay and small interfering RNA knockdown analysis. In addition, the antiobesity effects of PAN A were evaluated in C57BL/6J mice with high-fat diet (HFD)-induced obesity. Results: PAN A stimulated AMPK signalling, induced nuclear translocation of the AMPKα2 subunit and activated PPARα/δ; LKB1, a kinase that lies upstream of AMPK, mediated these effects. PAN A stimulated the direct binding of the AMPKα2 subunit to PPARα/δ, but PPARδ activation required direct interaction with PPARγ coactivator 1α (PGC-1α). Further, PAN A (50 mg/kg/day) reduced weight gain, fat mass, fatty liver and improved serum lipid profiles in obese mice. Additionally, PAN A reduced ectopic fat accumulation and increased the proportion of slow-twitch myofibres and mitochondria content in skeletal muscle, thereby increasing running endurance. Conclusions: PAN A, an LKB1-dependent AMPK stimulator, activated PPARα/δ and attenuated HFD-induced obesity and dysregulation of lipid metabolism. Our findings suggest that PAN A is a potent AMPK activator and show a novel molecular mechanism for the treatment of metabolic disorders.

Original languageEnglish
Pages (from-to)584-593
Number of pages10
JournalDiabetes, Obesity and Metabolism
Volume13
Issue number7
DOIs
Publication statusPublished - 2011 Jul

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint Dive into the research topics of 'Therapeutic potential of panduratin A, LKB1-dependent AMP-activated protein kinase stimulator, with activation of PPARα/δ for the treatment of obesity'. Together they form a unique fingerprint.

  • Cite this