| dc.description.abstract | In vitro studies suggest that fatty acid bind protein 1 (Fabp1) and sterol carrier protein
2/sterol carrier protein x (Scp2/Scpx) gene products facilitate the uptake, metabolism and
detoxification of dietary phytol in mammals. In fact, individually ablating FABP1 or SCP2/SCPx
each impairs hepatic branched-chain fatty acid uptake and/or metabolism. Studies also suggest
that singly ablating Fabp1 or Scp2/Scpx genes may exacerbate the impact of a high fat diet on
whole body phenotype and non-alcoholic fatty liver disease (NAFLD). However, concomitant
upregulation of FABP1 in SCP2/SCPx null mice complicates interpretation of each protein’s
physiological role in studies where only one of these proteins has been ablated. Therefore, the
impact of ablating both Fabp1 and Scp2/Scpx genes was explored in phytol and high fat diet fed
mice.
In the phytol study, triple gene ablation (TKO) increased hepatic total lipid accumulation,
primarily phospholipid, by mechanisms involved in increasing hepatic levels of proteins in the
phospholipid synthesis pathway while reducing expression of proteins in targeting fatty acids
towards the triacylglycerol synthesis pathway. Concomitantly, TKO also reduced expression of
proteins in targeting fatty acids towards the triacylglycerol synthesis pathway. In the high fat
study, wild type (WT) male mice exhibited higher hepatic lipid accumulation than WT females
and TKO increased hepatic lipid accumulation in both. The greater hepatic lipid accumulation in
WT males was associated with high hepatic expression of enzymes in glyceride synthesis, higher
hepatic bile acids and upregulation of transporters involved in hepatic reuptake of serum bile
acids. The TKO-induced increases in hepatic glycerides were attributed to sex dependent
upregulation of hepatic lipogenic enzymes.
Overall, since individually ablating the Scp2/Scpx gene elicits the upregulation of the
FABP1 protein, these findings with TKO mice help to resolve the contributions of Scp2/Scpx
gene ablation on dietary phytol and high fat induced whole body and hepatic lipid phenotype
independent of concomitant upregulation of FABP1. | en |
