Impact of gene ablation (TKO) on hepatic phytol metabolism in mice.

Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x () and liver fatty acid binding protein [ (L-FABP)] gene products facilitate hepatic uptake and metabolism of lipotoxic dietary phytol. However, interpretation of physiological function in mice singly gene ablated in the has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: ) An 8-anilino-1-naphthalenesulfonic acid displacement assay showed that neither SCP-2 nor L-FABP bound phytol, but both had high affinity for its metabolite, phytanic acid; ) GC-MS studies with phytol-fed WT and gene ablated [triple KO (TKO)] mice showed that TKO exacerbated hepatic accumulation of phytol metabolites in vivo in females and less so in males. Concomitantly, dietary phytol increased hepatic levels of total long-chain fatty acids (LCFAs) in both male and female WT and TKO mice. Moreover, in both WT and TKO female mice, dietary phytol increased hepatic ratios of saturated/unsaturated and polyunsaturated/monounsaturated LCFAs, while decreasing the peroxidizability index. However, in male mice, dietary phytol selectively increased the saturated/unsaturated ratio only in TKO mice, while decreasing the peroxidizability index in both WT and TKO mice. These findings suggested that: ) SCP-2 and FABP1 both facilitated phytol metabolism after its conversion to phytanic acid; and ) SCP-2/SCP-x had a greater impact on hepatic phytol metabolism than FABP1.