Dietary n-3 PUFA deprivation for 15 weeks upregulates elongase and desaturase expression in rat liver but not brain.
Fifteen weeks of dietary n-3 PUFA deprivation increases coefficients of conversion of circulating alpha-linolenic acid (alpha-LNA; 18:3n-3) to docosahexaenoic acid (DHA; 22:6n-3) in rat liver but not brain. To determine whether these increases reflect organ differences in enzymatic activities, we examined brain and liver expression of converting enzymes and of two of their transcription factors, peroxisome proliferator-activated receptor alpha (PPARalpha) and sterol-regulatory element binding protein-1 (SREBP-1), in rats fed an n-3 PUFA "adequate" (4.6% alpha-LNA of total fatty acid, no DHA) or "deficient" (0.2% alpha-LNA, no DHA) diet for 15 weeks after weaning. In rats fed the deficient compared with the adequate diet, mRNA and activity levels of Delta5 and Delta6 desaturases and elongases 2 and 5 were upregulated in liver but not brain, but liver PPARalpha and SREBP-1 mRNA levels were unchanged. In rats fed the adequate diet, enzyme activities generally were higher in liver than brain. Thus, differences in conversion enzyme expression explain why the liver has a greater capacity to synthesize DHA from circulating alpha-LNA than does the brain in animals on an adequate n-3 PUFA diet and why liver synthesis capacity is increased by dietary deprivation. These data suggest that liver n-3 PUFA metabolism determines DHA availability to the brain when DHA is absent from the diet.
Igarashi
Miki
M
Brain Physiology and Metabolism Section, National Institute on Aging, NIH, Bethesda, MD 20892, USA. mikii@mail.nih.gov
Ma
Kaizong
K
Chang
Lisa
L
Bell
Jane M
JM
Rapoport
Stanley I
SI
D000123:Acetyltransferases / Q000096:biosynthesis*; D042962:Acyl-CoA Oxidase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology*; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004281:Docosahexaenoic Acids / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000096:biosynthesis*; D000081031:Fatty Acid Elongases; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D008099:Liver / Q000201:enzymology*; D008297:Male; D047493:PPAR alpha / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D015854:Up-Regulation; D017962:alpha-Linolenic Acid / Q000378:metabolism
D004041:Dietary Fats; D015525:Fatty Acids, Omega-3; D047493:PPAR alpha; D012333:RNA, Messenger; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids; D044943:Fatty Acid Desaturases; D042962:Acyl-CoA Oxidase; D000123:Acetyltransferases; D000081031:Fatty Acid Elongases; D002334:Carnitine O-Palmitoyltransferase