Ovariectomy and 17β-estradiol alter transcription of lipid metabolism genes and proportions of neo-formed n-3 and n-6 long-chain polyunsaturated fatty acids differently in brain and liver.
Hormonal and nutritional factors regulate the metabolism of long-chain polyunsaturated fatty acids (LC-PUFA). We aimed to determine whether ovarian hormones influence the capacity of rats to synthesize the end-products 22:6n-3 (DHA) and 22:5n-6 (n-6DPA) from their respective dietary precursors (18:3n-3 and 18:2n-6), and can regulate PUFA conversion enzymes gene transcription in brain and/or liver. Females born with a low DHA status were fed from weaning to 8 weeks of age a diet providing both essential precursors, and were concurrently submitted to sham-operated control (SOC) or ovariectomy (OVX) in combination with or without 17β-estradiol (E2) dosed at 8 or 16 μg/day. Relative to SOC, OVX increased the hepatic Δ9-, Δ6- and Δ5-desaturase transcripts and cognate transcription factors (PPARα, PPARγ, RXRα, RARα), but it did not affect LC-PUFA contents in phospholipids. In comparison with SOC and OVX groups, both E2 doses prevented the increase of transcripts, while paradoxically augmenting DHA and n-6DPA in liver phospholipids. Thus, in the liver of rats undergoing ovariectomy, changes of LC-PUFA synthesizing enzyme transcripts and of LC-PUFA proportions were not correlated. In brain, ovariectomy did not modify the transcripts of lipid metabolism genes, but it decreased DHA (-15%) and n-6DPA (-28%). In comparison with SOC and OVX groups, ovariectomized females treated with E2 preserved their status of both LC-PUFA in brain and had increased transcripts of E2 receptor β, PPARδ, RARα and LC-PUFA synthesizing enzymes. In conclusion, E2 sustained the transcription of lipid metabolism genes and proportions of neo-formed DHA and n-6DPA differently in brain and liver.
Institut National de la Recherche Agronomique, Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales (UR 909), Département Alimentation Humaine, F-78352 Jouy-en-Josas, France. jean-marc.alessandri@jouy.inra.fr
Jean-Marc
JM
Alessandri
Audrey
A
Extier
Kaïs H
KH
Al-Gubory
Bénédicte
B
Langelier
Charlotte
C
Baudry
Claire
C
LePoupon
Monique
M
Lavialle
Philippe
P
Guesnet
D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D005260:Female; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D009928:Organ Specificity; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D004967:Estrogens; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D014157:Transcription Factors; D004958:Estradiol