Half‐lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n‐3 polyunsaturated fatty acids

Abstract

Male rat pups (21 days old) were placed on a diet deficient in n-3 polyunsaturated fatty acids (PUFAs) or on an n-3 PUFA adequate diet containing a-linolenic acid (a-LNA; 18 : 3n-3). After 15 weeks on a diet, [4, H]docosahexaenoic acid (DHA; 22 : 6n-3) was injected into the right lateral cerebral ventricle, and the rats were killed at fixed times over a period of 60 days. Compared with the adequate diet, 15 weeks of n-3 PUFA deprivation reduced plasma DHA by 89% and brain DHA by 37%; these DHA concentrations did not change thereafter. In the n-3 PUFA adequate rats, DHA loss half-lives, calculated by plotting log 10 (DHA radioactivity) against time after tracer injection, equaled 33 days in total brain phospholipid, 23 days in phosphatidylcholine, 32 days in phosphatidylethanolamine, 24 days in phosphatidylinositol and 58 days in phosphatidylserine; all had a decay slope significantly greater than 0 (p < 0.05). In the n-3 PUFA deprived rats, these half-lives were prolonged twofold or greater, and calculated rates of DHA loss from brain, J out , were reduced. Mechanisms must exist in the adult rat brain to minimize DHA metabolic loss, and to do so even more effectively in the face of reduced n-3 PUFA availability for only 15 weeks.

RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

“…In agreement with this suggestion, one study reported a decrease in brain mRNA expression of DHA-selective iPLA 2 in 24-and 30-month-old rats compared to 4-month-old animals and an increase in pro-inflammatory thromboxane A 2 concentration (Aid and Bosetti 2007), suggesting increased brain DHA half-life due to reduced consumption and upregulated AA metabolism during aging, respectively (DeMar et al 2004). The implication of altered brain AA and DHA metabolism with age on brain PUFA concentrations is controversial since some but not all studies reported age-related changes in PUFA composition in rodents and postmortem human brain (Soderberg et al 1990;Lopez et al 1995;Favrelere et al 2000;Giusto et al 2002).…”

“…A decreased liver synthesis-secretion rate of DHA and the corresponding reduction in plasma unesterified concentration may affect brain PUFA metabolism by decreasing brain DHA consumption and increasing vulnerability to neuroinflammation associated with upregulated AA metabolism, as reported in rats on a low n-3 PUFA diet, which also reduces plasma unesterified DHA concentration (DeMar et al 2004;Rao et al 2007;Kim et al 2011a). In agreement with this suggestion, one study reported a decrease in brain mRNA expression of DHA-selective iPLA 2 in 24-and 30-month-old rats compared to 4-month-old animals and an increase in pro-inflammatory thromboxane A 2 concentration (Aid and Bosetti 2007), suggesting increased brain DHA half-life due to reduced consumption and upregulated AA metabolism during aging, respectively (DeMar et al 2004).…”

“…Knowing concentrations of unesterified α-LNA and LA is particularly important for understanding liver synthesis of longer chain n-3 (including DHA) and n-6 (including AA) PUFAs, since unesterified but not esterified fatty acids are selectively incorporated into brain (Purdon et al 1997;Smith and Nagura 2001;DeMar et al 2004;Rahman et al 2010). Although this study focused on n-3 PUFA kinetics and concentrations, future studies should test the effects of aging on n-6 PUFA liver kinetics.…”

“…Newly synthesized DHA in liver is secreted into the plasma in triglyceride and phospholipid-rich lipoproteins, which can undergo lipolysis by a DHA-selective endothelial lipase (Chen and Subbaiah 2007). The resulting unesterified DHA can enter the brain to replace DHA lost due to metabolism (DeMar et al 2004). In one human study, incorporation of orally-administered 13 C-DHA into plasma esterified and unesterified fatty acid pools increased with age (Plourde et al 2011), suggesting age-related changes in whole-body including liver DHA metabolism and changes in the liver's capacity to maintain plasma esterified and unesterified DHA concentrations.…”

Chronic Lithium Chloride Administration Attenuates Brain NMDA Receptor-Initiated Signaling via Arachidonic Acid in Unanesthetized Rats

“…Replacement is proportional to PLA 2 activation and can be imaged by injecting radiolabeled AA intravenously, then measuring regional brain radioactivity by quantitative autoradiography. A regional AA incorporation coefficient k* (regional brain radioactivity/integrated plasma radioactivity), calculated in this way, has been shown to be independent of changes in cerebral blood flow and to represent the plasmaderived AA reincorporated into brain phospholipid (Basselin et al, 2003;Chang et al, 1997;DeGeorge et al, 1991;DeMar et al, 2004a;Rapoport, 2001Rapoport, , 2003Robinson et al, 1992).…”