Maternal liver docosahexaenoic acid (DHA) stores are increased via higher serum unesterified DHA uptake in pregnant long Evans rats

Metherel, Adam H.; Kitson, Alex P.; Domenichiello, Anthony F.; Lacombe, R.J. Scott; Hopperton, Kathryn E.; Trépanier, Marc-Olivier; Alashmali, Shoug; Lin, Lin; Bazinet, Richard P.

doi:10.1016/j.jnutbio.2017.05.011

Cited by 17 publications

(10 citation statements)

References 44 publications

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“…This observation and shifts in the n-3 PUFA pool in the liver and plasma toward higher amounts of DHA and fewer n-3 PUFA precursors suggest that increased DHA biosynthesis during pregnancy through upregulated FADS2 supports the production of 16:0/DHA PC. In our model, we showed that DHA increases in maternal plasma during pregnancy, which has been observed previously in humans (5)(6)(7)(8) and rats (14,42). In rats, the increase in plasma DHA occurs primarily in late pregnancy, as we and others (42) found an increase in DHA in plasma at 20 days of pregnancy, but not earlier (12-15 days of pregnancy).…”

Section: Discussionsupporting

confidence: 87%

“…This appears to be based on placental transfer studies and documented maternal lipidemia (2,7,11); however, the importance of DHA accumulation in plasma phospholipids has been documented (43). The focus on NEFA and TAG has also led to a focus on maternal adipose stores as a mobilizable source of DHA during pregnancy (2,14), despite the fact that these lipid pools tend to have relatively low concentrations of DHA (42,44,45). Our acyl species analysis indicating the specific increase in plasma 16:0/ DHA PC suggests considerable hepatic involvement of DHA mobilization and a mechanism where DHA enrichment of PC in the lipoprotein monolayer may be a delivery mechanism.…”

Section: Discussionmentioning

confidence: 99%

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PEMT, Δ6 desaturase, and palmitoyldocosahexaenoyl phosphatidylcholine are increased in rats during pregnancy

Chalil

Kitson

Henao

et al. 2018

Journal of Lipid Research

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DHA is important for fetal neurodevelopment. During pregnancy, maternal plasma DHA increases, but the mechanism is not fully understood. Using rats fed a fixed-formula diet (DHA as 0.07% total energy), plasma and liver were collected for fatty acid profiling before pregnancy, at 15 and 20 days of pregnancy, and 7 days postpartum. Phosphatidylethanolamine methyltransferase (PEMT) and enzymes involved in PUFA synthesis were examined in liver. Ad hoc transcriptomic and lipidomic analyses were also performed. With pregnancy, DHA increased in liver and plasma lipids, with a large increase in plasma DHA between day 15 and day 20 that was mainly attributed to an increase in 16:0/DHA phosphatidylcholine (PC) in liver (2.6-fold) and plasma (3.9-fold). Increased protein levels of Δ6 desaturase (FADS2) and PEMT at day 20 and increased expression and PEMT activity at day 15 suggest that during pregnancy, both DHA synthesis and 16:0/DHA PC synthesis are upregulated. Transcriptomic analysis revealed minor changes in the expression of genes related to phospholipid synthesis, but little insight on DHA metabolism. Hepatic PEMT appears to be the mechanism for increased plasma 16:0/DHA PC, which is supported by increased DHA biosynthesis based on increased FADS2 protein levels.

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Section: Discussionsupporting

confidence: 87%

Section: Discussionmentioning

confidence: 99%

PEMT, Δ6 desaturase, and palmitoyldocosahexaenoyl phosphatidylcholine are increased in rats during pregnancy

Chalil

Kitson

Henao

et al. 2018

Journal of Lipid Research

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“…As such, future studies utilizing our infusion and kinetic modeling techniques could provide real-time measures of turnover and half-life in response to changes in dietary n-3 PUFA intakes. Furthermore, we recently showed that pregnant rats do not have higher daily synthesis-secretion rates compared with age-matched virgin controls (15). Combined with no change in whole-body DHA stores, this suggests a potential increase in the half-life of DHA during pregnancy as a means to increase DHA availability to the developing fetus, a question that could be answered with our current model.…”

Section: Discussionmentioning

confidence: 66%

“…However, measures of downstream n-3 PUFA turnover from ALA can be difficult to interpret, as the tracer becomes diluted as it travels through the pathway and may not result in a true measure of DHA turnover. As a result, turnover and half-life of newly synthesized DHA from ALA by these calculations would be significantly underestimated and overestimated, respectively (14,15). To address this, we co-infused 2 H 5 -ALA and 13 C 22 -DHA to compare the turnover rate of DHA from plasma unesterified ALA compared with the turnover rate from plasma unesterified DHA.…”

Section: Discussionmentioning

confidence: 99%

Complete assessment of whole-body n-3 and n-6 PUFA synthesis-secretion kinetics and DHA turnover in a rodent model

Metherel

Lacombe

Chouinard-Watkins

et al. 2018

Journal of Lipid Research

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Previous assessments of the PUFA biosynthesis pathway have focused on DHA and arachidonic acid synthesis. Here, we determined whole-body synthesis-secretion kinetics for all downstream products of PUFA metabolism, including direct measurements of DHA and n-6 docosapentaenoic acid (DPAn-6, 22:5n-6) turnover, and compared n-6 and n-3 homolog kinetics. We infused labeled α-linolenic acid (ALA, 18:3n-3), linoleic acid (LNA, 18:2n-6), DHA, and DPAn-6 as H-ALA, C-LNA, C-DHA, and C-DPAn-6. Eight 11-week-old Long Evans rats fed a 10% fat diet were infused with the labeled PUFAs over 3 h, and plasma enrichment of labeled products was measured every 30 min. The DHA synthesis-secretion rate (94 ± 34 nmol/day) did not differ from other PUFA products (range, 21.8 ± 4.3 nmol/day to 408 ± 116 nmol/day). Synthesis-secretion rates of n-6 and n-3 PUFA homologs were similar, except 22:4n-6 and DPAn-6 had lower synthesis rates. However, daily turnover from newly synthesized DHA (0.067 ± 0.023%) was 56-fold to 556-fold slower than all other PUFA turnover and was 130-fold slower than that determined directly from the total plasma unesterified DHA pool. In conclusion, n-6 and n-3 PUFA synthesis-secretion kinetics suggest that differences in turnover, not in synthesis-secretion rates, primarily determine PUFA plasma levels.

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“…However, EPA and DHA are difficult to measure directly. The fatty acid methyl esterification is often considered for the measurement of EPA and DHA content in fish oil via potassium hydroxide transesterification [21], methyl esterification [22], boron trifluoride methylation [23], and sulfate methylation [24]. The above-mentioned literature was used to improve the determination of fatty acids in cod-liver oil.…”

Section: Introductionmentioning

confidence: 99%

Cod-Liver Oil Improves Metabolic Indices and hs-CRP Levels in Gestational Diabetes Mellitus Patients: A Double-Blind Randomized Controlled Trial

Yang

Lin

et al. 2019

Journal of Diabetes Research

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Objective. To investigate the effects of cod-liver oil on metabolic status and high-sensitivity C-reactive protein (hs-CRP) in patients with gestational diabetes mellitus (GDM). Methods. This study was a randomized, double-blinded, placebo-controlled trial with the allocation ratio of 1 : 1. The contents of EPA and DHA in cod-liver oil were measured using a gas chromatograph. A total of 550 GDM patients were randomly divided into the intervention group (cod-liver oil) and the control group (placebo, mineral oil), and both groups were given regular dietary care. Glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), lipid profiles, homeostatic model assessment insulin resistance (HOMA-IR), and hs-CRP were measured. Primary outcomes were different in HbA1c, FPG, 2hPG, and HOMA-IR between the two groups after 4-week randomization. Secondary outcomes were the blood glucose levels and perinatal complications (pregnancy-induced hypertension, polyhydramnios, premature delivery, postpartum hemorrhage, postpartum infection, premature rupture of membranes, and cesarean section) between the two groups before and after 12-16 weeks of cod-liver oil intervention from middle pregnancy to late pregnancy. Results. EPA and DHA were the main components of cod-liver oil with 76 mg/mL and 150 mg/mL, respectively. There was no significant difference for primary outcomes in the levels of HbA1c, FPG, 2hPG, HOMA-IR, and lipid profiles between the two groups (P>0.05). For the secondary outcomes, the levels of HbA1c, FPG, 2hPG, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol ratio (LDL-C), HOMA-IR, and hs-CRP in the intervention group were significantly lower than those in the control group (P<0.05). The incidence of perinatal complications in the intervention group was lower than that in the control group too (P<0.05). Conclusions. Cod-liver oil consumption effectively reduced the levels of blood glucose, lipid levels, hs-CRP, and HOMA-IR and the incidence of perinatal complications.

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Maternal liver docosahexaenoic acid (DHA) stores are increased via higher serum unesterified DHA uptake in pregnant long Evans rats

Cited by 17 publications

References 44 publications

PEMT, Δ6 desaturase, and palmitoyldocosahexaenoyl phosphatidylcholine are increased in rats during pregnancy

PEMT, Δ6 desaturase, and palmitoyldocosahexaenoyl phosphatidylcholine are increased in rats during pregnancy

Complete assessment of whole-body n-3 and n-6 PUFA synthesis-secretion kinetics and DHA turnover in a rodent model

Cod-Liver Oil Improves Metabolic Indices and hs-CRP Levels in Gestational Diabetes Mellitus Patients: A Double-Blind Randomized Controlled Trial

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