Sex-dependent impact of Scp-2/Scp-x gene ablation on hepatic phytol metabolism

Arch Biochem Biophys. 2017 Dec 1:635:17-26. doi: 10.1016/j.abb.2017.10.011. Epub 2017 Oct 16.

Abstract

While prior studies focusing on male mice suggest a role for sterol carrier protein-2/sterol carrier protein-x (SCP-2/SCP-x; DKO) on hepatic phytol metabolism, its role in females is unresolved. This issue was addressed using female and male wild-type (WT) and DKO mice fed a phytoestrogen-free diet without or with 0.5% phytol. GC/MS showed that hepatic: i) phytol was absent and its branched-chain fatty acid (BCFA) metabolites were barely detectable in WT control-fed mice; ii) accumulation of phytol as well as its peroxisomal metabolite BCFAs (phytanic acid » pristanic and 2,3-pristenic acids) was increased by dietary phytol in WT females, but only slightly in WT males; iii) accumulation of phytol and BCFA was further increased by DKO in phytol-fed females, but much more markedly in males. Livers of phytol-fed WT female mice as well as phytol-fed DKO female and male mice also accumulated increased proportion of saturated straight-chain fatty acids (LCFA) at the expense of unsaturated LCFA. Liver phytol accumulation was not due to increased SCP-2 binding/transport of phytol since SCP-2 bound phytanic acid, but not its precursor phytol. Thus, the loss of Scp-2/Scp-x contributed to a sex-dependent hepatic accumulation of dietary phytol and BCFA.

Keywords: Branched-chain fatty acids; Liver; Mice; Phytol; SCP-2; SCP-x.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Female
  • Gene Silencing
  • Lipid Metabolism / physiology*
  • Liver / metabolism*
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phytanic Acid / analogs & derivatives*
  • Phytanic Acid / metabolism
  • Phytol / administration & dosage
  • Phytol / pharmacokinetics*
  • Sex Factors

Substances

  • Carrier Proteins
  • sterol carrier proteins
  • Phytanic Acid
  • Phytol
  • phytenic acid