文章基本信息
- 标题：A phytol-enriched diet induces changes in fatty acid metabolism in mice both via PPAR{alpha}-dependent and -independent pathways
- 本地全文：下载
- 作者：Gloerich, J. ; van Vlies, N. ; Jansen, G. A. 等
- 期刊名称：JLR Papers In Press
- 印刷版ISSN：0022-2275
- 电子版ISSN：1539-7262
- 出版年度：2005
- 卷号：46
- 期号：04
- 页码：716-726
- DOI：10.1194/jlr.M400337-JLR200
- 出版社：American Society for Biochemistry and Molecular Biology
- 摘要：Branched-chain fatty acids (such as phytanic and pristanic acid) are ligands for the nuclear hormone receptor peroxisome proliferator-activated receptor
(PPAR) in vitro. To investigate the effects of these physiological compounds in vivo, wild-type and PPAR-deficient (PPAR–/–) mice were fed a phytol-enriched diet. This resulted in increased plasma and liver levels of the phytol metabolites phytanic and pristanic acid. In wild-type mice, plasma fatty acid levels decreased after phytol feeding, whereas in PPAR–/– mice, the already elevated fatty acid levels increased. In addition, PPAR–/– mice were found to be carnitine deficient in both plasma and liver. Dietary phytol increased liver free carnitine in wild-type animals but not in PPAR–/– mice. Investigation of carnitine biosynthesis revealed that PPAR is likely involved in the regulation of carnitine homeostasis. Furthermore, phytol feeding resulted in a PPAR-dependent induction of various peroxisomal and mitochondrial ß-oxidation enzymes. In addition, a PPAR-independent induction of catalase, phytanoyl-CoA hydroxylase, carnitine octanoyltransferase, peroxisomal 3-ketoacyl-CoA thiolase, and straight-chain acyl-CoA oxidase was observed.
In conclusion, branched-chain fatty acids are physiologically relevant ligands of PPAR in mice. These findings are especially relevant for disorders in which branched-chain fatty acids accumulate, such as Refsum disease and peroxisome biogenesis disorders.
Abbreviations: AMACR, -methylacyl-CoA racemase; BB, 
-butyrobetaine; BBD, -butyrobetaine dioxygenase; BCOX, branched-chain acyl-CoA oxidase; CAT, carnitine acetyltransferase; COT, carnitine octanoyltransferase; CPT2, carnitine palmitoyltransferase 2; CYP4A1, cytochrome P450 hydroxylase 4A1; DBP, D-bifunctional protein; Elovl, long-chain fatty acid elongase; ESI, electrospray ionization; LBP, L-bifunctional protein; LCAD, long-chain acyl-CoA dehydrogenase; MCAD, medium-chain acyl-CoA dehydrogenase; MTP, mitochondrial trifunctional protein; PhyH, phytanoyl-CoA hydroxylase; PMP70, peroxisomal membrane protein 70; PPAR, peroxisome proliferator-activated receptor; SBCHAD, short branched-chain 3-hydroxyacyl-CoA dehydrogenase; SCAD, short-chain acyl-CoA dehydrogenase; SCHAD, short-chain 3-hydroxyacyl-CoA dehydrogenase; SCOX, straight-chain acyl-CoA oxidase; SCPx, sterol carrier protein x; THIO, peroxisomal 3-ketoacyl-CoA thiolase; TMABADH, trimethylaminobutyraldehyde dehydrogenase; TML, trimethyllysine; VLCAD, very long-chain acyl-CoA dehydrogenase; VLCFA, very long-chain fatty acid
Supplementary key words peroxisome proliferator-activated receptor • peroxisomes • mitochondria • fatty acid ß-oxidation • very long-chain fatty acids • branched-chain fatty acids • acylcarnitines • peroxisomal disorders
