Metabolomic analysis of simvastatin and fenofibrate intervention in high-lipid diet-induced hyperlipidemia rats

Xu, Qi; Liu, Yinhui; Zhang, Qi; Ma, Bo; Yang, Zhen‐Dong; Liu, Lei; Yao, Di; Cui, Guangbo; Sun, Jian-he; Wu, Zimei

doi:10.1038/aps.2014.72

Cited by 47 publications

(37 citation statements)

References 44 publications

(52 reference statements)

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“…This reduction in plasma urea concentration may be associated with a lower protein catabolism or alternatively with an increase in the efficiency of nitrogen utilization [37] when feeding a high-fat, high-fibre diet. Similarly to our results, hyperlipidaemia induced by a high-fat diet was associated with a lower plasma level of tyrosine in rats [38,39]. Tyrosine is formed from the essential amino acid phenylalanine, which could explain the lower plasma level of this latter amino acid in pigs fed the HF diet than in pigs fed the LF diet [40].…”

Section: Discussionsupporting

confidence: 89%

NMR-based metabolomics highlights differences in plasma metabolites in pigs exhibiting diet-induced differences in adiposity

et al. 2015

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Section: Discussionsupporting

confidence: 89%

NMR-based metabolomics highlights differences in plasma metabolites in pigs exhibiting diet-induced differences in adiposity

et al. 2015

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“…Similarly, a significant increase in the atrial blood lactate level was observed during acute AF (van Bragt et al , ). Fenofibrate was reported to significantly decrease the level of BOH in high‐lipid diet rats (Xu et al , ). We demonstrated that AF induced a marked increase in the circulating lactate, AcAc, BOH and TKB levels in rabbits subjected to rapid‐pacing for 1 week.…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR‐α/sirtuin 1/PGC‐1α pathway

Liu

Hou

Yuan

et al. 2016

British J Pharmacology

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BACKGROUND AND PURPOSEAtrial metabolic remodelling is critical for the process of atrial fibrillation (AF). The PPAR-α/sirtuin 1 /PPAR co-activator α (PGC-1α) pathway plays an important role in maintaining energy metabolism. However, the effect of the PPAR-α agonist fenofibrate on AF is unclear. Therefore, the aim of this study was to determine the effect of fenofibrate on atrial metabolic remodelling in AF and explore its possible mechanisms of action. EXPERIMENTAL APPROACHThe expression of metabolic proteins was examined in the left atria of AF patients. Thirty-two rabbits were divided into sham, AF (pacing with 600 beats·min À1 for 1 week), fenofibrate treated (pretreated with fenofibrate before pacing) and fenofibrate alone treated (for 2 weeks) groups. HL-1 cells were subjected to rapid pacing in the presence or absence of fenofibrate, the PPAR-α antagonist GW6471 or sirtuin 1-specific inhibitor EX527. Metabolic factors, circulating biochemical metabolites, atrial electrophysiology, adenine nucleotide levels and accumulation of glycogen and lipid droplets were assessed. KEY RESULTSThe PPAR-α/sirtuin 1/PGC-1α pathway was significantly inhibited in AF patients and in the rabbit/HL-1 cell models, resulting in a reduction of key downstream metabolic factors; this effect was significantly restored by fenofibrate. Fenofibrate prevented the alterations in circulating biochemical metabolites, reduced the level of adenine nucleotides and accumulation of glycogen and lipid droplets, reversed the shortened atrial effective refractory period and increased risk of AF. CONCLUSION AND IMPLICATIONSFenofibrate inhibited atrial metabolic remodelling in AF by regulating the PPAR-α/sirtuin 1/PGC-1α pathway. The present study may provide a novel therapeutic strategy for AF. AbbreviationsAcAc, acetoacetate; AERP, atrial effective refractory period; AF, atrial fibrillation; BOH, β-hydroxybutyrate; FFA, free fatty acid; GLUT4, glucose transporter 4; GS1, glycogen synthase1; H-FABP, heart fatty acid binding protein; MCAD, medium-chain acylCoA dehydrogenase; mCPT-1, mitochondrial carnitine palmitoyltransferase1; PDH, pyruvate dehydrogenase; PDK4, pyruvate dehydrogenase kinase 4; PGC-1α, PPAR co-activator 1α; p-GS1, phosphorylated-GS1; TKB, total ketone body

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“…; Ozório ; Xu et al . ). In general, although blood glucose concentration of fish is in a dynamic equilibrium due to the regulation by the nervous and endocrine systems, but it is quite easy to change (Imsland et al .…”

Section: Regulation Of L‐carnitine On Nutrients Metabolism In Aquaticmentioning

confidence: 97%

The metabolic regulation of dietary L‐carnitine in aquaculture nutrition: present status and future research strategies

Limbu

et al. 2018

Reviews in Aquaculture

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L-carnitine is a multi-functional nutrient which plays a leading role in fatty acid metabolism in mammals and other eukaryotes. Its main physiological function is to promote fatty acid b-oxidation to produce energy, which reduces body fat content and improves body weight without affecting moisture content in whole body and muscle. In recent years, its dietary supplementation in aquaculture nutrition has been studied in different cultured species. It has been proved that L-carnitine can improve growth and increase lipid utilization rate in some aquatic animals. However, such beneficial effects of dietary L-carnitine are limited or absent in other species. The reasons for the conflicting results obtained on L-carnitine functions in aquatic animals need to be elucidated. This review explores comprehensively the different physiological functions of L-carnitine in various aquatic animals. In the end, research strategies are provided to elucidate the existing conflicts on dietary L-carnitine application in aquaculture nutrition in order to promote its utilization in aquatic feed industry.

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Metabolomic analysis of simvastatin and fenofibrate intervention in high-lipid diet-induced hyperlipidemia rats

Abstract: A series of potential biomarkers including tyrosine, creatinine, linoleic acid, β-hydroxybutyric acid and ornithine have been identified by metabolomic profiling, which may be used to identify the metabolic changes during hyperlipidemia progression.

Cited by 47 publications

References 44 publications

NMR-based metabolomics highlights differences in plasma metabolites in pigs exhibiting diet-induced differences in adiposity

NMR-based metabolomics highlights differences in plasma metabolites in pigs exhibiting diet-induced differences in adiposity

Fenofibrate inhibits atrial metabolic remodelling in atrial fibrillation through PPAR‐α/sirtuin 1/PGC‐1α pathway

The metabolic regulation of dietary L‐carnitine in aquaculture nutrition: present status and future research strategies

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