Abstract
Background: Methods to increase the amount of omega-3 (n-3) PUFAs in milk are desirable for neonatal health. The n-3 PUFA, α-linolenic acid (18:3n-3), can be elongated to EPA (20:5n-3) and DHA (22:6n-3). n-6 PUFAs suppress tissue n-3 PUFA incorporation, but the effect of SFAs is not clear. Objectives: In this study, we compared the effects of SFAs and n-6 PUFAs on n-3 PUFA incorporation into milk and tissues of lactating mice and tissues of their offspring. Methods: Female CD-1 mice were bred at 8 wk of age. All experimental diets included 3% flaxseed oil and were begun on day 8 of lactation: low-fat diet (LFD); high-SFA diet (SAT), with an additional 12% saturated oil; or high-linoleic-acid diet (HLA), with 12% high-linoleic-acid oil (% kcal, carbohydrates:fat:protein: LFD, 49:24:27; both SAT and HLA, 35:46:19; n = 5/treatment). After 5 d, pup stomach milk clot FA profiles, tissue FA profiles in dams and pups, and mammary and hepatic expression of lipid metabolism genes in dams were analyzed. Data were analyzed by ANOVA with treatment diet as a fixed effect. Results: Dams in all groups had similar total milk fat concentrations, but both SAT and HLA decreased the concentration of n-3 PUFAs (SAT: -23%; HLA: -31%) compared with LFD, and HLA increased milk n-6 FAs by 347% compared with SAT. SAT pups had n-3 PUFA tissue concentrations similar to LFD, but HLA pups had lower n-3 PUFAs than SAT pups in multiple tissues (liver, -32%; kidney, -29%; heart, -28%; muscle, -18%). Mammary expression of lipid metabolism genes was mostly unchanged, but hepatic expression of elongases and desaturases was decreased with SAT compared with LFD [elongation of very-long-chain fatty acid (Elov)5, -42%; Elov6, -64%; fatty acid desaturase (Fads)1, -33%; Fads2, -44%]. Conclusions: HLA decreased n-3 PUFA concentrations across multiple pup tissues compared with SAT. This suggests that high dietary n-6 PUFAs suppress n-3 PUFA incorporation in neonates.
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Key Points
Other dietary FAs may compete with n–3 PUFAs for digestion, absorption, tissue uptake, enzyme binding, and incorporation into phospholipid membranes and milk fat globules. Abundant n–6 PUFAs, such as linoleic acid (LA; 18:2n–6), shift the binding of desaturase enzymes, especially the delta-6 desaturase (FADS2), toward production of AA from LA rather than EPA and DHA from ALA. Dietary oleic acid (18:1n–9) in laying hens decreases n–3 PUFA incorporation into egg yolk, suggesting MUFAs may also compete with n–3 PUFAs for incorporation. It is unclear if SFAs suppress EPA and DHA synthesis.
The lactating mouse provides an ideal model for investigation of n–3 PUFA incorporation into milk and neonatal tissues, because FA profiles in suckling pups can be readily assessed. Measuring tissue FA profiles in dams and pups reveals how n–3 PUFAs are partitioned during the neonatal period and how milk FA profile affects n–3 PUFA status. Incorporation of n–3 PUFAs into pup tissues represents the most biologically relevant outcome, because the goal of optimizing milk n–3 PUFAs is to increase their availability to neonates. Rodent milk includes higher concentrations of the mid-chain FAs from de novo lipogenesis than human milk but concentrations of the VLC n–3 and n–6 PUFAs are comparable with human milk. Although high-fat diets rich in both SFA and LA suppressed milk n–3 PUFAs, tissue EPA and DHA incorporation was most suppressed in pups whose mothers were fed the HLA compared with SAT. This indicates that high dietary n–6 PUFAs may interfere with neonatal n–3 PUFA tissue incorporation. Treatment effects were tissue-specific. Brain tissue was protected from suppression of DHA, and brain EPA was lower in pups from dams fed HLA. However, other pup tissues showed suppression of both EPA and DHA in dams fed HLA compared with SAT. There were minimal changes in lipid metabolism enzymes in the mammary gland, but Fads and Elov genes were suppressed in the liver with SAT. These results indicate that dietary PUFAs, not endogenous synthesis, are the primary drivers of milk PUFA composition and that elevated milk n–6 PUFAs suppress neonatal tissue incorporation of n–3 PUFAs.