Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 Jan;58(1):111-123.
doi: 10.1194/jlr.M070862. Epub 2016 Nov 18.

Both Maternal and Offspring Elovl2 Genotypes Determine Systemic DHA Levels in Perinatal Mice

Affiliations
Free PMC article

Both Maternal and Offspring Elovl2 Genotypes Determine Systemic DHA Levels in Perinatal Mice

Anna M Pauter et al. J Lipid Res. .
Free PMC article

Abstract

The molecular details relevant to dietary supplementation of the omega-3 fatty acid DHA in mothers as well as in their offspring are not clear. The PUFA elongase, elongation of very long-chain fatty acid (ELOVL)2, is a critical enzyme in the formation of DHA in mammals. In order to address the question regarding the origin of DHA during perinatal life, we have used DHA-deficient Elovl2-ablated mice as a model system to analyze the maternal impact on the DHA level in their offspring of various genotypes. Elovl2-/- mothers maintained on control diet had significantly lower systemic levels of DHA compared with the Elovl2+/- and Elovl2+/+ mothers. Dietary DHA administration during the pregnancy and lactation periods led to increased DHA accretion in maternal tissues and serum of all genotypes. The proportion of DHA in the liver and serum of the Elovl2-/- offspring was significantly lower than in the Elovl2+/+ offspring. Remarkably, the DHA level in the Elovl2+/- offspring nursed by DHA-free-fed Elovl2-/- mothers was almost as high as in +/+ pups delivered by +/+ mothers, suggesting that endogenous synthesis in the offspring can compensate for maternal DHA deficiency. Maternal DHA supplementation had a strong impact on offspring hepatic gene expression, especially of the fatty acid transporter, Mfsd2a, suggesting a dynamic interplay between DHA synthesis and DHA uptake in the control of systemic levels in the offspring.

Keywords: docosahexaenoic acid; docosahexaenoic acid synthesis; elongation of very long-chain fatty acid 2; lactation; polyunsaturated fatty acid; pregnancy; supplementation.

Figures

Fig. 1.
Fig. 1.
Effects of Elovl2 genotype and dietary DHA on the maternal body weight at postpartum stage. Body weight (A) measured at the end of experiment and delta body weight (B) of the weight at the beginning and the end of experiment for Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) mothers and control females fed either control diet (Control) or DHA-enriched diet (DHA). Results are presented as mean ± SEM of two to five mice. Statistical significances are shown between groups, ***P < 0.001.
Fig. 2.
Fig. 2.
Effects of maternal and offspring genotype and maternal diet on the offspring body weight. Body weight (A) expressed in grams and obesity index (B) expressed as a ratio of fat mass/lean mass of suckling offspring with Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) genotypes delivered by Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) mothers fed either control diet (Control) or DHA-enriched diet (DHA) measured at postnatal days 14–18 (moment they were euthanized) (A) and postmortem (B) after dissection of some organs. Results are presented as mean ± SEM of two to five mice.
Fig. 3.
Fig. 3.
Maternal DHA accretion through pregnancy and lactation is affected by Elovl2 genotype and dietary DHA. Proportion of DHA (22:6n-3) in the liver (A), serum (B), mammary glands (C), and WAT (D) of Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) mothers and control females fed either control diet (Control) or DHA-enriched diet (DHA) expressed as percent of total fatty acids. For the percent of remaining fatty acids, see respectively, supplemental Tables S16–S19. Results are presented as mean ± SEM of two to five mice. #Represents a log2 absolute fold change >1 between control (Control) and DHA-enriched (DHA) diet, unless specified.
Fig. 4.
Fig. 4.
The correlation of DHA level across different tissues changes with pregnancy and lactation. Scatter plots across different tissues of mothers and control females representing correlation for DHA level between serum and liver (A), liver and mammary gland (MG) (B), serum and mammary gland (C), mammary gland and WAT (D), liver and WAT (E), and serum and WAT (F).
Fig. 5.
Fig. 5.
DHA accretion in the liver and serum of offspring depends on both maternal and offspring genotype and the maternal dietary DHA. Proportion of DHA (22:6n-3) in the liver (A) and serum (B) of offspring with Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) genotype delivered by Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) mothers fed either control diet (Control) or DHA-enriched diet (DHA) expressed as a percent of total fatty acids. For the percent of remaining fatty acids, see respectively, supplemental Tables S20, S21. Results are presented as means ± SEM of two to five mice (A) or as pooled samples from three to five individuals (B). *Represents statistical significance (P < 0.05) between genotypes; #Represents statistical significance (P < 0.05) between control (Control) and maternal DHA-enriched diet (DHA).
Fig. 6.
Fig. 6.
Hepatic gene expression of PUFA synthesizing enzymes. Expression of Elovl2 (A), Elovl5 (B), Fads1 (C), and Fads2 (D) in the liver of offspring with Elovl2+/+ (+/+), Elov2+/− (+/−), and Elovl2−/− (−/−) genotype delivered by Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) mothers fed either control diet (Control) or DHA-enriched diet (DHA) expressed as relative mRNA levels (target gene/18S). Results are presented as mean ± SEM of two to five mice. *P < 0.05, **P < 0.01, ***P < 0.001.
Fig. 7.
Fig. 7.
Analyses of lipogenic gene expression of Fas (A), Srebp-1c (B), Scd1 (C), and the DHA transporter Mfsd2a (D) in the liver of offspring with Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) genotype delivered by Elovl2+/+ (+/+), Elovl2+/− (+/−), and Elovl2−/− (−/−) mothers fed either control diet (Control) or DHA-enriched diet (DHA) expressed as relative mRNA levels (target gene/18S). Results are presented as mean ± SEM of two to five mice. *P < 0.05, **P < 0.01, ***P < 0.001.
Fig. 8.
Fig. 8.
Maternal and offspring Elovl2 genotype and maternal diet contribute to DHA accretion through perinatal life.

Similar articles

See all similar articles

Cited by 5 articles

LinkOut - more resources

Feedback