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  • 标题:Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in mice
  • 本地全文:下载
  • 作者:Stephen M. Storey ; Huan Huang ; Avery L. McIntosh
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2017
  • 卷号:58
  • 期号:6
  • 页码:1153-1165
  • DOI:10.1194/jlr.M075457
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要: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.
  • 关键词:fatty acid binding protein 1/sterol carrier protein-2/sterol carrier protein-x ; triple knockout ; peroxisomal oxidation
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