Key Findings:
Arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3) are important for brain health. Deficiency may lead to cognitive and behavioral defects in development and aging. This study showed that normal brain DHA content can be maintained through conversion in the liver of ALA to circulating DHA, as long as there is enough dietary ALA. Further the brain’s ability for conversion is very low. Increased expression of liver elongases and desaturases occurred in the liver but not brain when ALA is limited. This research found that following deficiency of omega 3 fatty acids for 15 weeks, DHA loss from brain was slowed and the expression of DHA-metabolizing enzymes was reduced, both of which conserved brain DHA. The findings are significant with regard to the debate about ALA conversion to DHA and show that when conversion needs to be up-regulated, the liver has the capacity to do so.
ABSTRACT:
Plasma alpha-linolenic acid (a-LNA, 18:3n-3) and linoleic acid (LA, 18:2n-6) do not contribute significantly to the brain content of docosahexaenoic acid (DHA,22:6n-3) or arachidonic acid (AA,20:4n-6), respectively, and neither DHA nor AA can be synthesized de novo in vertebrate tissue. Therefore, measured rates of incorporation of circulating DHA and AA into brain exactly represent their rates of consumption by brain. Positron emission tomography (PET) has been used to show, based on this information, that the adult human brain consumes AA and DHA at rates of 17.8 and 4.6 mg/day, respectively, and that AA consumption does not change significantly with age. In unanesthetized adult rats fed an n-3 PUFA ‘‘adequate’’ diet containing 4.6% a-LNA (of total fatty acids) as its only n-3 PUFA, the rate of liver synthesis of DHA was more than sufficient to maintain brain DHA, whereas the brain’s rate of DHA synthesis is very low and unable to do so. Reducing dietary a-LNA in the DHA-free diet led to up regulation of liver but not brain coefficients of a-LNA conversion to DHA and of liver expression of elongases and desaturases that catalyze this conversion. Concurrently, brain DHA loss slowed due to down regulation of several of its DHA-metabolizing enzymes. Dietary a-LNA deficiency also promoted accumulation of brain docosapentaenoic acid (22:5n-6), and up regulated expression of AA metabolizing enzymes, including cytosolic and secretory phospholipases A 2 and cyclooxygenase-2. These changes, plus reduced levels of brain derived neurotrophic factor (BDNF) and cAMP response element-binding protein (CREB) in n-3 PUFA diet deficient rats, likely render their brain more vulnerable to neuropathological insults. (Author’s abstract)