Kinetic analysis of cardiac transcriptome regulation during chronic high-fat diet in dogs.
In the present study, we investigated, using custom dog cDNA arrays, the time course of transcriptional changes in the left ventricle of dogs fed a normal diet or a high-fat diet (HFD) for 9-24 wk. Array hybridizations were performed with complex probes representing mRNAs expressed in left ventricles from obese hypertensive and lean control dogs. We identified 63 differentially expressed genes, and expression of 17 of 20 randomly chosen genes was confirmed by real-time PCR. Transcripts were categorized into groups involved in metabolism, cell signaling, tissue remodeling, ionic regulation, cell proliferation, and protein synthesis. Hierarchical clustering indicated that the pattern of coregulated genes depends on duration of the HFD, suggesting that HFD-induced obesity hypertension is associated with continuous cardiac transcriptome adaptation despite stability of both body weight and blood pressure. GenMAPP analysis of the data pointed out the crucial importance of the ventricle TGF-beta pathway. Our results suggest that this system may be involved in molecular remodeling during HFD and in changes observed in the transcription profile, reflecting functional and morphological abnormalities that arise during prolonged HFD. These results also suggest some novel regulatory pathways for cardiac adaptation to obesity.
Philip-Couderc
Pierre
P
Unité de Recherches sur les Obésités, Institut National de la Santé et de la Recherche Médicale U586, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France.
Smih
Fatima
F
Hall
John E
JE
Pathak
Atul
A
Roncalli
Jérome
J
Harmancey
Romain
R
Massabuau
Pierre
P
Galinier
Michel
M
Verwaerde
Patrick
P
Senard
Jean-Michel
JM
Rouet
Philippe
P
D000818:Animals; D016000:Cluster Analysis; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology*; D004285:Dogs; D005786:Gene Expression Regulation / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000235:genetics / Q000503:physiopathology; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D013851:Thinness / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D016276:Ventricular Function
D004041:Dietary Fats; D012333:RNA, Messenger