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Physiol. Genomics (June 29, 2004). doi:10.1152/physiolgenomics.00001.2004
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Submitted on January 5, 2004
Accepted on June 16, 2004

Kinetic analysis of cardiac transcriptome regulation during chronic high fat diet in dogs

Pierre Philip-Couderc1, Fatima Smih2, John E Hall3, Atul Pathak2, Jerome Roncalli2, Romain Harmancey2, Pierre Massabuau2, Michel Galinier2, Patrick Verwaerde2, Jean-Michel Senard2, and Philippe Rouet2*

1 Unite de Recherches sur les obesites, Universite Paul Sabatier, Institut National de la Sante et de la Recherche Medicale, (Inserm U586), Institut Louis Bugnard, Toulouse, France; Departement Neurosciences fondamentales, Centre Medical Universitaire, Geneve, Switzerland
2 Unite de Recherches sur les obesites, Universite Paul Sabatier, Institut National de la Sante et de la Recherche Medicale, (Inserm U586), Institut Louis Bugnard, Toulouse, France
3 Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS, USA

* To whom correspondence should be addressed. E-mail: Philippe.rouet{at}toulouse.inserm.fr.

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 to 24 weeks. Array hybridizations were performed with complex probes representing mRNAs expressed in left ventricles from obese hypertensive and lean control dogs. 63 differentially expressed genes were identified 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 co-regulated 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.




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