Dietary n-6 PUFA deprivation downregulates arachidonate but upregulates docosahexaenoate metabolizing enzymes in rat brain.
BACKGROUND
Dietary n-3 polyunsaturated fatty acid (PUFA) deprivation increases expression of arachidonic acid (AA 20:4n-6)-selective cytosolic phospholipase A(2) (cPLA(2)) IVA and cyclooxygenase (COX)-2 in rat brain, while decreasing expression of docosahexaenoic acid (DHA 22:6n-3)-selective calcium-independent iPLA(2) VIA. Assuming that these enzyme changes represent brain homeostatic responses to deprivation, we hypothesized that dietary n-6 PUFA deprivation would produce changes in the opposite directions.


METHODS
Brain expression of PUFA-metabolizing enzymes and their transcription factors was quantified in male rats fed an n-6 PUFA adequate or deficient diet for 15weeks post-weaning.


RESULTS
The deficient compared with adequate diet increased brain mRNA, protein and activity of iPLA(2) VIA and 15-lipoxygenase (LOX), but decreased cPLA(2) IVA and COX-2 expression. The brain protein level of the iPLA(2) transcription factor SREBP-1 was elevated, while protein levels were decreased for AP-2α and NF-κB p65, cPLA(2) and COX-2 transcription factors, respectively.


CONCLUSIONS
With dietary n-6 PUFA deprivation, rat brain PUFA metabolizing enzymes and some of their transcription factors change in a way that would homeostatically dampen reductions in brain n-6 PUFA concentrations and metabolism, while n-3 PUFA metabolizing enzyme expression is increased. The changes correspond to reported in vitro enzyme selectivities for AA compared with DHA.
National Institute on Aging, National Institutes of Health, Bethesda, MD, USA. kimhyung@mail.nih.gov
Hyung-Wook
HW
Kim
Jagadeesh S
JS
Rao
Stanley I
SI
Rapoport
Miki
M
Igarashi
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D004032:Diet; D004041:Dietary Fats / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D015536:Down-Regulation; D043371:Fatty Acids, Omega-6 / Q000172:deficiency*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D010105:Oxygenases / Q000378:metabolism; D054467:Phospholipases A2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation
D004041:Dietary Fats; D043371:Fatty Acids, Omega-6; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D010088:Oxidoreductases; D010105:Oxygenases; D054467:Phospholipases A2