Rat heart cannot synthesize docosahexaenoic acid from circulating α-linolenic acid because it lacks elongase-2

Igarashi, Miki; Ma, Kaizong; Chang, Lisa; Bell, Jane M.; Rapoport, Stanley I.

doi:10.1194/jlr.m800093-jlr200

Cited by 59 publications

(67 citation statements)

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“…Since liver-synthesized DHA can get into brain and retina after being hydrolyzed from circulating lipoproteins ( 29,50 ), hepatic synthesis has the potential of supplying the brain's DHA. Additionally, the rat heart cannot synthesize either ␣ -LNA or EPA to DHA, since it lacks elongase 2 (M. Igarashi et al, unpublished observations) ( 10 ), so that in the absence of dietary DHA, liver synthesis is the only source of heart DHA. These observations indicate that EPA could exert a central or cardiac action via the DHA formed from it in the liver.…”

Section: W I T H D Rmentioning

confidence: 99%

Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats

Gao

Kiesewetter

Chang

et al. 2009

Journal of Lipid Research

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( 5-7 ), bipolar disorder ( 8 ), and other human brain disorders. DHA also is considered important for optimum cardiac function ( 9 ), but it cannot be synthesized from its n-3 PUFA precursors in the heart due to a lack of elongase-2 ( 10 ).Some but not all clinical studies have indicated that dietary fi sh and marine oils that contain DHA and eicosapentaenoic acid (EPA), as well as dietary DHA or EPA given alone, can reduce brain or heart disease ( 7,(11)(12)(13)(14)(15)(16). Some of the EPA effects on these organs could be direct, as dietary EPA can lower plasma triacylglycerol ( 17,18 ), is a more potent platelet inhibitor than DHA ( 19,20 ), and its products have strong anti-infl ammatory effects ( 21 ). Other EPA effects may be indirect, through its conversion to DHA in the liver ( 22 ). Studies using compartmental analysis in humans ( 23 ) and in rats ( 24 ) fed ␣ -linolenic acid ( ␣ -LNA; 18:3n-3) or EPA labeled with a stable isotope reported that both ␣ -LNA and EPA were converted to DHA.To date, the rate of liver conversion of EPA to secreted DHA has not been quantifi ed directly in the intact organism. Knowing this rate in humans might help to estimate daily dietary requirements of . To measure this rate in rats for the fi rst time, in this article we employed a published method that was used to determine whole-body DHA synthesis secretion from circulating ␣ -LNA ( 29 ) in unanesthetized adult rats on an n-3 PUFAcontaining diet. [U-13 C]EPA was infused intravenously for 2 h, which allowed the establishment of a steady-state DHA synthesis secretion after about 1 h. Operational equations were used to calculate whole-body synthesis secretion rates of esterifi ed docosapentaenoic acid (DPA) and DHA and Abstract Dietary docosahexaenoic acid (DHA; 22:6n-3) and eicosapentaenoic acid (EPA; 20:5n-3) are considered important for maintaining normal heart and brain function, but little EPA is found in brain, and EPA cannot be elongated to DHA in rat heart due to the absence of elongase-2. Ingested EPA may have to be converted in the liver to DHA for it to be fully effective in brain and heart, but the rate of conversion is not agreed on. This rate was determined in male adult rats fed a standard n-3 PUFA, containing diet by infusing unesterifi ed albumin-bound [U- C]EPA intravenously for 2 h and measuring esterifi ed [13 C]labeled PUFAs in arterial plasma lipoproteins, as well as the specifi c activity of unesterifi ed plasma EPA. Whole-body (presumably hepatic) synthesis secretion rates from circulating unesterifi ed EPA, calculated from peak fi rst derivatives of plasma esterifi ed concentration × volume curves, equaled 2.61 mol/day for docosapentaenoic acid (22:5n-3) and 5.46 mol/day for DHA. The DHA synthesis rate was 24-fold greater than the reported brain DHA consumption rate in rats. Thus, dietary EPA could help to maintain brain and heart DHA homeostasis because it is converted at a relatively high rate in the liver to circulating DHA. -Gao, F., D. Kiesewetter, L. Chang, K. Ma, S. I. Rapoport, and M. Igara...

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Section: W I T H D Rmentioning

confidence: 99%

Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats

Gao

Kiesewetter

Chang

et al. 2009

Journal of Lipid Research

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“…DHA may be obtained directly from dietary sources, such as fish or fish products, or it can be synthesized from its nutritionally essential plant-derived precursor, α-linolenic acid (18:3n-3, α-LNA), through a series of elongation and desaturation steps (Sprecher 2000). The major site of DHA synthesis is the liver, whereas brain or heart synthesis is much less (Scott and Bazan 1989;Demar et al 2005;Igarashi et al 2007;Igarashi et al 2008;Rapoport et al 2010).…”

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confidence: 99%

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

Gao

Taha

et al. 2012

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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.

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“…Unlike ∆5, ∆6 and ∆9 desaturases, the elongases do not display uniform responce to fish oil or PPARα agonist. 48 For example; rat heart does not synthesize DHA from α-LNA owing to the absence of elongase-2, but must obtain its DHA entirely from plasma.…”

Section: Discussionmentioning

confidence: 99%

Effects of n–3 Supplementation on Plasma and Liver Phospholipid Fatty Acids Profile in Aged Wistar Rats

Popović¹,

Borozan²,

Arsić³

et al. 2011

Croat. Chem. Acta

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Abstract. The effects of fish oil supplementation in Wistar rats are focused on cardiovascular, endocrine, metabolic and antioxidant status changes. We determined plasma and liver phospholipid fatty acids (FAs) status and plasma lipid concentrations in aged Wistar rats. Our results showed differences in plasma and liver FAs profiles as well as plasma chlolesterol (CHOL), triglicerides (TG), high density lipoproteins (HDL), low density lipoproteins (LDL), CHOL/HDL ratio (risk factor for atherosclerosis) and LDL/HDL ratio (risk for cardiovascular diseases) between treated and control group of animals. In fish oil treated group there were statistically significant changes in FAs profile in increasing linoleic acid (LA), dihomo-γ linoleic acid, eicopentanoic acid (EPA) and docosapentaenoic acid (DPA) and decreasing in arachidonic acid (AA) concentration. Also, liver phospholipids FAs results showed increasing concentrations of vascenic acid, LA, EPA, and DPA and decreasing concentration of AA after supplementation of fish oil compared to control group. However, concentrations of CHOL, LDL and non HDL concentrations decreased while HDL increased in fish oil group. CHOL/HDL, LDL/HDL ratios decreased. These findings suggest that long term treatment of fish oil in aged Wistar rats can be beneficial in decreasing LDL, and decreasing risk factors for developing atherosclerosis and cardiovascular diseases. (doi: 10.5562/cca1751)

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Rat heart cannot synthesize docosahexaenoic acid from circulating α-linolenic acid because it lacks elongase-2

Cited by 59 publications

References 59 publications

Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats

Whole-body synthesis secretion of docosahexaenoic acid from circulating eicosapentaenoic acid in unanesthetized rats

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

Effects of n–3 Supplementation on Plasma and Liver Phospholipid Fatty Acids Profile in Aged Wistar Rats

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