RETRACTED ARTICLE: Aging decreases rate of docosahexaenoic acid synthesis-secretion from circulating unesterified α-linolenic acid by rat liver

Abstract

Docosahexaenoic acid (DHA,, an n-3 polyunsaturated fatty acid (PUFA) found at high concentrations in brain and retina and critical to their function, can be obtained from fish products or be synthesized from circulating α-linolenic acid (α-LNA, 18:3n-3) mainly in the liver. With aging, liver synthetic enzymes are reported reduced or unchanged in the rat. To test whether liver synthesis-secretion of DHA from α-LNA changes with age, we measured whole-body DHA conversion coefficients and rates in unanesthetized adult male Fischer-344 rats aged 10, 20, or 30 months, fed an eicosapentaenoic acid (EPA, 20:5n-3)-and DHAcontaining diet. Unesterified [U-13 C]α-LNA bound to albumin was infused intravenously for 2 h, while [ 13 C]-esterified n-3 PUFAs were measured in arterial plasma, as were unlabeled unesterified and esterified PUFA concentrations. Plasma unesterified n-3 PUFA concentrations declined with age, but esterified n-3 PUFA concentrations did not change significantly. Calculated conversion coefficients were not changed significantly with age, whereas synthesis-secretion rates (product of conversion coefficient and unesterified plasma α-LNA concentration) of esterified DHA and n-3 DPA were reduced. Turnovers of esterified n-3 PUFAs in plasma decreased with age, whereas half-lives increased. The results suggest that hepatic capacity to synthesize DHA and other n-3 PUFAs from circulating α-LNA is maintained with age in the rat, but that reduced plasma α-LNA availability reduces net synthesis-secretion. As unesterified plasma DHA is the form that is incorporated preferentially into brain phospholipid, its reduced synthesis may be deleterious to brain function in aged rats.

Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats

“…Using the steady-state infusion method, we estimated synthesis rates of DHA from ALA to be 1.5 and 0.045 μmol/day in animals consuming the ALA and control diets, respectively. These rates are lower, but in line with previously published estimates using the steady-state infusion technique ( 24 , 43 , 44 ). Differences could be due to the fact that we performed the steady-state infusion in rats fed a diet containing 2% of the total fatty acids as ALA, whereas Gao et al ( 24 ) fed their animals a diet containing approximately 5% of the total fatty acids as ALA.…”

“…This rate is only a measure of the synthesis rate in these rats at this time, when the rats are older and when the DHA synthesis rate is also likely low. It has been shown previously that the DHA synthesis rate decreases with age in rats ( 44 ).…”

Intake of n-3 Polyunsaturated Fatty Acids Increases Omega-3 Index in Aged Male and Female Spontaneously Hypertensive Rats

“…Women also have a greater capacity than man to synthesise n-3 PUFA from their essential fatty acid precursor ALA [ 12 ]. Moreover, turnover of n-3 PUFA in plasma of old males decreased with age [ 13 ]. Furthermore, we have found strain- and sex-related differences in red blood cells levels of ALA, which was almost three times higher in female SHR than age-matched Wistar rats and comparing to males.…”

Fatty acid transporting proteins: Roles in brain development, aging, and stroke

“…Several studies have suggested that the aging brain (22 month-old) is prone to lose DHA in rodents [24, 25]. The specific DHA deficiency in aged brain may result from an age-related reduction in the activity of the enzymes specifically regulating DHA synthesis in liver, as well as its uptake and assembly into brain phospholipids [26–28]. Despite the age-related loss of DHA observed in rodents, dietary supplementation of DHA in aged rats can prevent such losses [29, 30].…”