title: Cinnamaldehyde Contributes to Insulin Sensitivity by Activating PPARδ, PPARγ, and RXR.
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.
authors.affiliation: Department of Chinese Medicine, Shaanxi Provincial People's Hospital, Xi'an 710068, China.|Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Juan-E
authors.initials: JE
authors.lastname: Li
authors.affiliation: Department of Medicine and Clinical Science, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Futawaka
authors.affiliation: Department of Medicine and Clinical Science, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Nephrology and Blood Purification, Institute of Biomedical Research and Innovation, Kobe Medical Frontier Center, Kobe 650-0047, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Tagami
authors.affiliation: Graduate School, Beijing University of Chinese Medicine, Beijing 100029, China.
authors.forename: Tong-Hua
authors.initials: TH
authors.lastname: Liu
authors.affiliation: Department of Medicine and Clinical Science, School of Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan.|Clinical Research Institute, Kyoto Medical Center, National Hospital Organization, Kyoto 612-8555, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Moriyama
mesh_terms: D000171:Acrolein / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D017667:Adipocytes / Q000378:metabolism; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects*; D057809:HEK293 Cells; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D047494:PPAR delta / Q000235:genetics* / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D010642:Phenoxyacetates / Q000494:pharmacology; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000235:genetics; D047488:Retinoid X Receptors / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D045162:Thiazolidinediones / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D005227:Fatty Acids; D047494:PPAR delta; D047495:PPAR gamma; D010642:Phenoxyacetates; D012333:RNA, Messenger; D047488:Retinoid X Receptors; D045162:Thiazolidinediones; D000171:Acrolein; C012843:cinnamaldehyde; D000077205:Pioglitazone
keywords: Cinnamaldehyde; PPARs; RXR