Both maternal and offspring Elovl2 genotypes determine systemic DHA levels in perinatal mice

J Lipid Res. 2017 Jan;58(1):111-123. doi: 10.1194/jlr.M070862. Epub 2016 Nov 18.

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.

MeSH terms

  • Acetyltransferases / genetics*
  • Acetyltransferases / metabolism
  • Animals
  • Docosahexaenoic Acids / administration & dosage
  • Docosahexaenoic Acids / metabolism*
  • Fatty Acid Elongases
  • Female
  • Gene Expression Regulation
  • Genotype
  • Humans
  • Liver / metabolism*
  • Liver / pathology
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Knockout
  • Pregnancy
  • Symporters

Substances

  • ELOVL2 protein, human
  • ELOVL2 protein, mouse
  • Membrane Transport Proteins
  • Mfsd2a protein, mouse
  • Symporters
  • Docosahexaenoic Acids
  • Acetyltransferases
  • Fatty Acid Elongases