Effects of DHA dietary intervention on hepatic lipid metabolism in apolipoprotein E-deficient and C57BL/6J wild-type mice

Biomed Pharmacother. 2021 Dec:144:112329. doi: 10.1016/j.biopha.2021.112329. Epub 2021 Oct 13.

Abstract

Lipid metabolic disorder occurs when ApoE gene is deficient. However, the role of Docosahexaenoic acid (DHA) in relieving hepatic lipid metabolic disorder in apolipoprotein E-deficient (ApoE -/-) mice remains unknown. We fed 3-month-old C57BL/6J wild-type (C57 wt) and ApoE -/- mice respectively with normal or DHA fortified diet for 5 months. We found ApoE gene deficiency caused hepatic lipid deposition and increased lipid levels in plasma and liver. Hepatic gene expression of SRB1, CD36 and FABP5 in ApoE -/- mice, protein expression of HMGCR, LRP1 in C57 wt mice and protein expression of LRP1 in ApoE -/- mice increased after DHA intervention. In DHA-fed ApoE -/- mice, LXRα/β and PPARα protein expression down-regulated in cytoplasm, but LXRα/β protein expression up-regulated in nucleus. DHA treatment decreased RXRα and RXRβ expression in C57 wt and ApoE -/- female mice. Deletion of ApoE gene caused lipid metabolism disorder in liver of mice. DHA treatment efficiently meliorated lipid metabolism caused by ApoE deficient through the regulation of gene and protein expressions of molecules involved in liver fatty acids transport and lipid metabolism.

Keywords: Apolipoprotein E-deficient mice; DHA; Lipid metabolism; Liver; Non-alcoholic fatty liver disease.

MeSH terms

  • Administration, Oral
  • Animals
  • Dietary Supplements*
  • Docosahexaenoic Acids / administration & dosage*
  • Fatty Acid Transport Proteins / genetics
  • Fatty Acid Transport Proteins / metabolism
  • Gene Expression Regulation
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / genetics
  • Lipids / blood*
  • Liver / drug effects*
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout, ApoE

Substances

  • Fatty Acid Transport Proteins
  • Lipids
  • Docosahexaenoic Acids