El Kebbaj Riad, Andreoletti Pierre, El Hajj Hammam I, El Kharrassi Youssef, Vamecq Joseph, Mandard Stéphane, Saih Fatima-Ezzahra, Latruffe Norbert, El Kebbaj M'Hammed Saïd, Lizard Gérard, Nasser Boubker, Cherkaoui-Malki Mustapha
Univ. Bourgogne-Franche Comté, Laboratoire BioPeroxIL (Biochimie du Peroxysome, Inflammation et Métabolisme Lipidique), EA 7270, 21000 Dijon, France.
Laboratoir de Biochimie et Neurosciences, Faculté des Sciences et Techniques, Université Hassan I, BP 577, 26 000 Settat, Morocco.
Biochim Open. 2015 Oct 31;1:51-59. doi: 10.1016/j.biopen.2015.10.002. eCollection 2015.
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.
在脓毒症患者中，肝脏代谢及其为其他器官提供能量底物的能力受损。在注射纯化内毒素（脂多糖，LPS）的小鼠中再现了人类患者中出现的这种以及许多其他病理生理变化。在本研究中，用阿甘油进行营养干预对暴露于LPS的小鼠中参与肝脏脂肪酸氧化（FAOx）和糖异生的基因下调提出了挑战。在暴露于LPS之前，给小鼠喂食添加或不添加6%（w/w）阿甘油（AO）或6%（w/w）橄榄油（OO）的标准饲料，通过mRNA转录水平和/或酶活性评估肝脏基因表达。AO（或OO）食物补充表明，在LPS处理的小鼠中，参与FAOx和糖异生的基因的肝脏表达得以保留。这种预防性保护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）及其共激活因子过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC-1α）的基因表达恢复有关。AO对LPS诱导的代谢失调所传达的这些预防机制可能为人类脓毒症的管理增添新的治疗潜力。
