Argan oil prevents down-regulation induced by endotoxin on liver fatty acid oxidation and gluconeogenesis and on peroxisome proliferator-activated receptor gamma coactivator-1α, (PGC-1α), peroxisome proliferator-activated receptor α (PPARα) and estrogen related receptor α (ERRα)

Riad El Kebbaj , Pierre Andreoletti , Hammam I. El Hajj , Youssef El Kharrassi , Joseph Vamecq , Stéphane Mandard , Fatima-Ezzahra Saih , Norbert Latruffe , M'Hammed Saïd El Kebbaj , Gérard Lizard , Boubker Nasser , Mustapha Cherkaoui-Malki
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引用次数: 19

Abstract

In patients with sepsis, liver metabolism and its capacity to provide other organs with energetic substrates are impaired. This and many other pathophysiological changes seen in human patients are reproduced in mice injected with purified endotoxin (lipopolysaccharide, LPS). In the present study, down-regulation of genes involved in hepatic fatty acid oxidation (FAOx) and gluconeogenesis in mice exposed to LPS was challenged by nutritional intervention with Argan oil. Mice given a standard chow supplemented or not with either 6% (w/w) Argan oil (AO) or 6% (w/w) olive oil (OO) prior to exposure to LPS were explored for liver gene expressions assessed by mRNA transcript levels and/or enzyme activities. AO (or OO) food supplementation reveals that, in LPS-treated mice, hepatic expression of genes involved in FAOx and gluconeogenesis was preserved. This preventive protection might be related to the recovery of the gene expressions of nuclear receptors peroxisome proliferator-activated receptor α (PPARα) and estrogen related receptor α (ERRα) and their coactivator peroxisome proliferator-activated receptor gamma coactivator-1α, (PGC-1α). These preventive mechanisms conveyed by AO against LPS-induced metabolic dysregulation might add new therapeutic potentialities in the management of human sepsis.

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阿曼坚果油可抑制内毒素诱导的肝脏脂肪酸氧化和糖异生的下调以及过氧化物酶体增殖物激活受体- γ辅激活因子-1α (PGC-1α)、过氧化物酶体增殖物激活受体α (PPARα)和雌激素相关受体α (ERRα)的下调。
在脓毒症患者中,肝脏代谢及其向其他器官提供能量底物的能力受损。在注射了纯化内毒素(脂多糖,LPS)的小鼠中,这种和许多其他在人类患者中看到的病理生理变化也得以重现。在本研究中,用摩洛哥坚果油进行营养干预,以挑战LPS暴露小鼠肝脂肪酸氧化(FAOx)和糖异生相关基因的下调。研究人员通过mRNA转录水平和/或酶活性评估小鼠肝脏基因表达,在暴露于LPS之前,给小鼠标准饲料,或不添加6% (w/w)坚果油(AO)或6% (w/w)橄榄油(OO)。补充AO(或OO)食物表明,在lps处理的小鼠中,FAOx和糖异生相关基因的肝脏表达得以保留。这种预防作用可能与核受体过氧化物酶体增殖物激活受体α (PPARα)和雌激素相关受体α (ERRα)及其辅激活物过氧化物酶体增殖物激活受体γ辅激活因子-1α (PGC-1α)基因表达的恢复有关。这些由AO传达的预防机制可以对抗lps诱导的代谢失调,可能为人类败血症的治疗增加新的治疗潜力。
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