Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.

Intrauterine growth retardation increases the susceptibility of pigs to high-fat diet-induced mitochondrial dysfunction in skeletal muscle.
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DOI:
10.1371/journal.pone.0034835
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Zheng P
Zheng P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu J;Chen D;Yao Y;Yu B;Mao X;He J;Huang Z;Zheng P

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人们已经认识到,产前生长受限与晚年代谢相关疾病的发展之间存在关系,这是一个涉及线粒体功能障碍的过程。此外,宫内发育迟缓(IUGR)增加了后代对高脂(HF)饮食诱导的代谢综合征的易感性。最近的研究结果表明,HF喂养降低线粒体的氧化能力和受损的骨骼肌线粒体功能。因此,我们假设IUGR对线粒体生物发生和功能的长期影响使后代更容易受到HF饮食诱导的线粒体功能障碍的影响。正常出生体重(NBW)和IUGR猪被分配到控制或HF饮食在一个完全随机的设计,分别。饲养4周后,测定生长性能和与线粒体功能相关的分子途径。结果表明,IUGR降低了生长性能和血浆胰岛素浓度。在喂食HF饮食的后代中,IUGR与血浆瘦素水平升高、甘油三酯和丙二醛(MDA)浓度升高以及骨骼肌中糖原和ATP含量降低相关。高脂饲料喂养的IUGR子代表现出乳酸脱氢酶(LDH)和葡萄糖-6-磷酸脱氢酶(G6 PD)活性降低。IUGR猪代谢性状的这些改变伴随着线粒体呼吸功能受损,线粒体DNA(mtDNA)含量减少,以及负责线粒体生物发生和功能的基因的mRNA表达水平下调。总之,我们的研究结果表明,IUGR使后代更容易受到HF饮食诱导的线粒体功能障碍。
It has been recognized that there is a relationship between prenatal growth restriction and the development of metabolic-related diseases in later life, a process involved in mitochondrial dysfunction. In addition, intrauterine growth retardation (IUGR) increases the susceptibility of offspring to high-fat (HF) diet-induced metabolic syndrome. Recent findings suggested that HF feeding decreased mitochondrial oxidative capacity and impaired mitochondrial function in skeletal muscle. Therefore, we hypothesized that the long-term consequences of IUGR on mitochondrial biogenesis and function make the offspring more susceptible to HF diet-induced mitochondrial dysfunction. Normal birth weight (NBW), and IUGR pigs were allotted to control or HF diet in a completely randomized design, individually. After 4 weeks of feeding, growth performance and molecular pathways related to mitochondrial function were determined. The results showed that IUGR decreased growth performance and plasma insulin concentrations. In offspring fed a HF diet, IUGR was associated with enhanced plasma leptin levels, increased concentrations of triglyceride and malondialdehyde (MDA), and reduced glycogen and ATP contents in skeletal muscle. High fat diet-fed IUGR offspring exhibited decreased activities of lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G6PD). These alterations in metabolic traits of IUGR pigs were accompanied by impaired mitochondrial respiration function, reduced mitochondrial DNA (mtDNA) contents, and down-regulated mRNA expression levels of genes responsible for mitochondrial biogenesis and function. In conclusion, our results suggest that IUGR make the offspring more susceptible to HF diet-induced mitochondrial dysfunction.
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