氯贝丁酯可增加新生仔猪的长链脂肪酸氧化。

Clofibrate increases long-chain fatty acid oxidation by neonatal pigs.

作者信息

Bai Xiumei, Lin Xi, Drayton Josephine, Liu Yulan, Ji Cheng, Odle Jack

机构信息

Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC; and.

Laboratory of Developmental Nutrition, Department of Animal Science, North Carolina State University, Raleigh, NC; and

出版信息

J Nutr. 2014 Nov;144(11):1688-93. doi: 10.3945/jn.114.193169. Epub 2014 Sep 3.

DOI:10.3945/jn.114.193169

PMID:25332467

Abstract

BACKGROUND

Utilization of energy-dense lipid fuels is critical to the rapid development and growth of neonates.

OBJECTIVE

To increase efficiency of milk fat utilization by newborn pigs, the effect of clofibrate on in vivo and in vitro long-chain fatty acid (LCFA) oxidation was evaluated.

METHODS

Newborn male pigs were administered 5 mL of vehicle (2% Tween 80) with or without clofibrate (75 mg/kg body weight) once daily via i.g. gavage for 4 d. Total LCFA oxidative capacity was measured in respiration chambers after gastric infusion (n = 5 per treatment) with isoenergetic amounts of [1-(14)C]triglycerides (TGs), either oleic acid (18:1n-9) TG [3.02 mmol/kg body weight (BW)(0.75)] or erucic acid (22:1n-9) TG (2.46 mmol/kg BW(0.75)). Total expired (14)CO2 was collected and quantified at 20-min intervals over 24 h. Hepatic in vitro LCFA oxidation was determined simultaneously using [1-(14)C]oleic acid and erucic acid substrates.

RESULTS

The in vivo 24-h accumulative [1-(14)C]TG oxidation (percentage of energy intake/kg BW(0.75)) tended to increase with clofibrate supplementation (P = 0.10), although there was no difference in the peak or mean utilization rate. The maximal extent of oleic acid TG oxidation was 1.6-fold that of erucic acid TG (P < 0.006). Hepatic in vitro LCFA oxidation increased 61% with clofibrate (P < 0.0008). The increase in mitochondria was 4-fold greater than in peroxisomes. The relative abundance of mRNA increased 2- to 3-fold for hepatic peroxisome proliferator-activated receptor α and its target genes (fatty acyl-coenzyme A oxidase and carnitine palmitoyltransferase) in the pigs that were administered clofibrate (P < 0.04).

CONCLUSION

Clofibrate may improve in vivo LCFA oxidative utilization in neonatal pigs.

摘要

背景

利用能量密集型脂质燃料对新生儿的快速发育和成长至关重要。

目的

为提高新生仔猪乳脂肪的利用效率，评估氯贝丁酯对体内和体外长链脂肪酸（LCFA）氧化的影响。

方法

给新生雄性仔猪每天经口灌胃给予5 mL载体（2%吐温80），其中一组添加氯贝丁酯（75 mg/kg体重），另一组不添加，持续4天。在胃内灌注等能量的[1-(14)C]甘油三酯（TGs）后，在呼吸室中测量总LCFA氧化能力（每组n = 5），所灌注的TGs分别为油酸（18:1n-9）TG [3.02 mmol/kg体重（BW）(0.75)]或芥酸（22:1n-9）TG（2.46 mmol/kg BW(0.75)）。在24小时内每隔20分钟收集并定量呼出的总(14)CO2。同时使用[1-(14)C]油酸和芥酸底物测定肝脏体外LCFA氧化。

结果

补充氯贝丁酯后，体内24小时累积的[1-(14)C]TG氧化（能量摄入量/kg BW(0.75)的百分比）有增加趋势（P = 0.10），尽管峰值或平均利用率无差异。油酸TG氧化的最大程度是芥酸TG的1.6倍（P < 0.006）。氯贝丁酯使肝脏体外LCFA氧化增加61%（P < 0.0008）。线粒体的增加幅度比过氧化物酶体大4倍。在给予氯贝丁酯的仔猪中，肝脏过氧化物酶体增殖物激活受体α及其靶基因（脂肪酰辅酶A氧化酶和肉碱棕榈酰转移酶）的mRNA相对丰度增加了2至3倍（P < 0.04）。