营养性维生素A缺乏对大鼠心脏脂质代谢的影响：其与PPAR基因表达的关系。
Effect of nutritional vitamin A deficiency on lipid metabolism in the rat heart: Its relation to PPAR gene expression.
作者信息
Vega Verónica Analía, Anzulovich Ana Cecilia, Varas Silvia Mabel, Bonomi Mirtha Ruth, Giménez María Sofía, Oliveros Liliana Beatriz
机构信息
Department of Biochemistry and Biological Sciences, National University of San Luis, and IMIBIO-SL, CONICET, Argentina.
出版信息
Nutrition. 2009 Jul-Aug;25(7-8):828-38. doi: 10.1016/j.nut.2009.01.008. Epub 2009 Apr 1.
OBJECTIVE
We studied the effect of dietary vitamin A deprivation on lipid composition and mRNA expression of regulatory enzymes involved in rat heart energetic lipid metabolism and its relation to the expression of peroxisome proliferator-activated receptor (PPAR) and retinoid X receptor (RXR) genes.
METHODS
Male Wistar 21-d-old rats were fed for 3 mo with a vitamin A-free diet (vitamin A-deficient group) and the same diet plus 8 mg of retinol palmitate per kilogram of diet (control group). One group of deficient animals received the control diet 15 d before sacrifice (vitamin A-refed group). Heart ventricular and mitochondrial lipid contents were determined. Lipid synthesis was measured using radioactive precursors and acetyl-coenzyme A carboxylase and mitochondrial carnitine palmitoyltransferase-I (CPT-I) activities using radioactive substrates. Fatty acid composition of mitochondrial phospholipids was analyzed by gas-liquid chromatography. Heart expression of acetyl-coenzyme A carboxylase, CPT-I, PPAR-alpha, PPAR-beta, RXR-alpha, and RXR-beta was assessed by reverse transcriptase polymerase chain reaction, and CPT-I expression was also measured by real-time polymerase chain reaction.
RESULTS
Vitamin A deficiency induced changes in heart ventricular lipid content and synthesis. Mitochondrial cardiolipin decreased and the proportion of phospholipids/saturated fatty acids increased. Heart activity and mRNA levels of CPT-I and expression of PPAR-alpha and PPAR-beta genes were enhanced, whereas acetyl-coenzyme A carboxylase activity diminished. Furthermore, vitamin A deficiency decreased heart mRNA levels of RXRs. Vitamin A refeeding reverted most of the observed changes.
CONCLUSION
Lipid metabolism is significantly modified in hearts of vitamin A-deficient rats. Alteration of mitochondrial energetic processes by modifying the activity and gene expressions of the regulatory enzymes is associated with a high PPAR expression induced by vitamin A deprivation.
目的
我们研究了饮食中维生素A缺乏对大鼠心脏能量脂质代谢相关调节酶的脂质组成和mRNA表达的影响，以及其与过氧化物酶体增殖物激活受体（PPAR）和视黄酸X受体（RXR）基因表达的关系。
方法
将21日龄雄性Wistar大鼠分为两组，一组喂食不含维生素A的饲料3个月（维生素A缺乏组），另一组喂食相同饲料但每千克饲料添加8毫克视黄醇棕榈酸酯（对照组）。一组缺乏维生素A的动物在处死前15天给予对照饲料（维生素A再喂养组）。测定心脏心室和线粒体脂质含量。使用放射性前体测量脂质合成，使用放射性底物测量乙酰辅酶A羧化酶和线粒体肉碱棕榈酰转移酶-I（CPT-I）活性。通过气液色谱分析线粒体磷脂的脂肪酸组成。通过逆转录聚合酶链反应评估心脏中乙酰辅酶A羧化酶、CPT-I、PPAR-α、PPAR-β、RXR-α和RXR-β的表达，同时通过实时聚合酶链反应测量CPT-I的表达。
结果
维生素A缺乏导致心脏心室脂质含量和合成发生变化。线粒体心磷脂减少，磷脂/饱和脂肪酸比例增加。CPT-I的心脏活性和mRNA水平以及PPAR-α和PPAR-β基因的表达增强，而乙酰辅酶A羧化酶活性降低。此外，维生素A缺乏降低了心脏中RXRs的mRNA水平。维生素A再喂养使大多数观察到的变化恢复。
结论
维生素A缺乏大鼠心脏中的脂质代谢发生显著改变。通过改变调节酶的活性和基因表达来改变线粒体能量过程与维生素A缺乏诱导的高PPAR表达有关。
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