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Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in mice.


ABSTRACT: Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (Scp-2/Scp-x) and liver fatty acid binding protein [Fabp1 (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 Scp-2/Scp-x has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: i) 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; ii) GC-MS studies with phytol-fed WT and Fabp1/Scp-2/SCP-x 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: 1) SCP-2 and FABP1 both facilitated phytol metabolism after its conversion to phytanic acid; and 2) SCP-2/SCP-x had a greater impact on hepatic phytol metabolism than FABP1.

SUBMITTER: Storey SM 

PROVIDER: S-EPMC5454513 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Impact of <i>Fabp1/Scp-2/Scp-x</i> gene ablation (TKO) on hepatic phytol metabolism in mice.

Storey Stephen M SM   Huang Huan H   McIntosh Avery L AL   Martin Gregory G GG   Kier Ann B AB   Schroeder Friedhelm F  

Journal of lipid research 20170414 6


Studies in vitro have suggested that both sterol carrier protein-2/sterol carrier protein-x (<i>Scp-2/Scp-x</i>) and liver fatty acid binding protein [<i>Fabp1</i> (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 <i>Scp-2/Scp-x</i> has been complicated by concomitant upregulation of FABP1. The work presented herein provides several novel insights: <i>i</i>) An 8-anili  ...[more]

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