Nutritional deprivation of alpha-linolenic acid decreases but does not abolish turnover and availability of unacylated docosahexaenoic acid and docosahexaenoyl-CoA in rat brain.
We applied our in vivo fatty acid method to examine concentrations, incorporation, and turnover rates of docosahexaenoic acid (22:6 n-3) in brains of rats subject to a dietary deficiency of alpha-linolenic acid (18:3 n-3) for three generations. Adult deficient and adequate rats of the F3 generation were infused intravenously with [4, 5-(3)H]docosahexaenoic acid over 5 min, after which brain uptake and distribution of tracer were measured. Before infusion, the plasma 22:6 n-3 level was 0.2 nmol ml(-1) in 18:3 n-3-deficient compared with 10.6 nmol ml(-1) in control rats. Brain unesterified 22:6 n-3 was not detectable, whereas docosahexaenoyl-CoA content was reduced by 95%, and 22:6 n-3 content in different phospholipid classes was reduced by 83-88% in deficient rats. Neither plasma or brain arachidonic acid (20:4 n-6) level was significantly changed with diet. Docosapentaenoic acid (22:5 n-6) reciprocally replaced 22:6 n-3 in brain phospholipids. Calculations using operational equations from our model indicated that 22:6 n-3 incorporation from plasma into brain was reduced 40-fold by 18:3 n-3 deficiency. Recycling of 22:6 n-3 due to deacylation-reacylation within phospholipids was reduced by 30-70% with the deficient diet, but animals nevertheless continued to produce 22:6 n-3 and docosahexaenoyl-CoA for brain function. We propose that functional brain effects of n-3 deficiency reflect altered ratios of n-6 to n-3 fatty acids.
Contreras
M A
MA
Section on Brain Physiology and Metabolism, National Institute on Aging, Bethesda 20892, USA. contrera@exchange.nih.gov
Greiner
R S
RS
Chang
M C
MC
Myers
C S
CS
Salem
N
N
Rapoport
S I
SI
D000214:Acyl Coenzyme A / Q000378:metabolism*; D000215:Acylation; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000378:metabolism*; D004032:Diet; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015525:Fatty Acids, Omega-3 / Q000097:blood; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D014316:Tritium; D017962:alpha-Linolenic Acid / Q000172:deficiency* / Q000378:metabolism
D000214:Acyl Coenzyme A; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D010743:Phospholipids; C044663:docosahexaenoyl-coenzyme A; D017962:alpha-Linolenic Acid; D014316:Tritium; D004281:Docosahexaenoic Acids