Hyperlipidic diets induce early alterations of the vitamin A signalling pathway in rat colonic mucosa.
OBJECTIVE
Dietary factors can be associated with colorectal cancer. Fatty acids modulate gene expression in various tissues, mediated by activation of the peroxisome proliferator activated receptor: PPAR. Vitamin A signalling is mediated by retinoic acid (RA) receptors (RAR) and retinoid X receptors (RXR). The steroid nuclear receptors PPAR, RAR, RXR, are DNA-binding proteins and they induce gene transcription upon activation by specific ligands and interacting with distinct promoter sequences in the target genes. The aim of this study was to investigate the impact of hyperlipidic diets on the expression of PPARg, RXRa and RARb mRNA in rat colon.


METHODS
Rats were fed during 4 weeks with the following diets: a cafeteria diet where 60% of the energy was supplied as lipids and a high fat diet (HFD) represented by 25% of a safflower oil (w/w) rich in polyunsaturated fatty acids, mainly n-6. Nuclear receptors mRNA were quantified by realtime RT-PCR with TaqMan probe process or SYBRGreen I chemical.


RESULTS
The cafeteria diet and the HFD induced a significant decrease in RARb mRNA: -36% (p<0.02) and -64% (P<0.001) respectively. Simultaneously, an increased expression of PPARg mRNA was observed for cafeteria diet +35% (P<0.05) and for HFD +45% (P<0.05). The level of RXRa mRNA was significantly increased for cafeteria diet: +53% (P<0.0002), while no significant difference in RXRa mRNA was observed in colonic mucosa rats whose fed with the 25% HFD.


CONCLUSIONS
These results showed that an hyperlipidic diet could induce early modifications in the pattern of expression of nuclear receptors in rat colon. Many mechanisms could be probably involved but one hypothesis is that a modification of the balance between the nuclear receptors, resulting from an increased expression of PPARg, could induce a decreased expression of RARb in rat colon.
Laboratory of Nutrition and Cellular Signalling, University Bordeaux 1, Avenue des Facultés, 33405 Talence-Cedex, France.
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Groubet
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Pallet
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Delage
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Redonnet
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Higueret
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Cassand
D000818:Animals; D052160:Benzothiazoles; D003106:Colon / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry; D003959:Diamines; D004041:Dietary Fats / Q000008:administration & dosage*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D009930:Organic Chemicals / Q000737:chemistry; D011804:Quinolines; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism*
D052160:Benzothiazoles; D003959:Diamines; D004041:Dietary Fats; D043371:Fatty Acids, Omega-6; D009930:Organic Chemicals; D011804:Quinolines; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014801:Vitamin A; C098022:SYBR Green I; D012313:RNA; D012321:DNA-Directed RNA Polymerases; C455879:Taq sigma A