RRC ID 38111
Author Li JE, Futawaka K, Yamamoto H, Kasahara M, Tagami T, Liu TH, Moriyama K.
Title Cinnamaldehyde Contributes to Insulin Sensitivity by Activating PPARδ, PPARγ, and RXR.
Journal Am. J. Chin. Med.
Abstract Cinnamon is a traditional folk herb used in Asia and has been reported to have antidiabetic effects. Our previous study showed that cinnamaldehyde (CA), a major effective compound in cinnamon, exhibited hypoglycemic and hypolipidemic effects together in db/db mice. The aim of the present study was to elucidate the molecular mechanisms of the effects of CA on the transcriptional activities of three peroxisome proliferator-activated receptors, (PPAR) α, δ, and γ. We studied the effects of CA through a transient expression assay with TSA201 cells, derivatives of human embryonic kidney cell line (HEK293). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was also performed to evaluate mRNA expression levels. We show here that CA induced PPARδ, PPARγ and retinoid X receptor (RXR) activation. CA may activate PPARγ in a different manner than pioglitazone, as CA selectively stimulated PPARγ S342A mutant while pioglitazone did not. In addition, CA and L-165041 had a synergistic effect on PPARδ activation. To gather the biological evidence that CA increases PPARs transcription, we further measured the expressions of PPARδ and PPARγ target genes in 3T3-L1 adipocytes. The data showed CA induced the expression of PPARδ and PPARγ target genes, namely aP2 and CD36, in differentiated adipocytes. As a result, PPARδ, PPARγ and their heterodimeric partner RXR appear to play a part in the CA action in the target tissues, thereby enhancing insulin sensitivity and fatty acid β-oxidation and energy uncoupling in skeletal muscle and adipose tissue.
Volume 43(5)
Pages 879-92
Published 2015
DOI 10.1142/S0192415X15500512
PMID 26227398
MeSH Acrolein / analogs & derivatives* Acrolein / isolation & purification Acrolein / pharmacology Adipocytes / metabolism Cinnamomum zeylanicum / chemistry* Drug Synergism Energy Metabolism / drug effects Fatty Acids / metabolism Gene Expression / drug effects* HEK293 Cells Humans Insulin Resistance / genetics* Muscle, Skeletal / metabolism Oxidation-Reduction / drug effects PPAR delta / genetics* PPAR delta / metabolism PPAR gamma / genetics* PPAR gamma / metabolism Phenoxyacetates / pharmacology Pioglitazone RNA, Messenger / genetics Retinoid X Receptors / genetics* Retinoid X Receptors / metabolism Reverse Transcriptase Polymerase Chain Reaction Stimulation, Chemical Thiazolidinediones / pharmacology Transcription, Genetic / drug effects* Up-Regulation / drug effects*
IF 3.51
Times Cited 13
Human and Animal Cells