Repetitive orogastric gavage affects the phenotype of diet-induced obese mice.
Repetitive orogastric gavage affects the phenotype of diet-induced obese mice.
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DOI：
10.1016/j.physbeh.2010.04.001
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发表时间：
2010-06-16
影响因子：
2.9
通讯作者：
Puder, Mark
中科院分区：
文献类型：
--
作者：
de Meijer, Vincent E.;Le, Hau D.;Meisel, Jonathan A.;Puder, Mark
关键词：
随着肥胖症的流行达到流行病的比例，对药物干预以对抗代谢综合征及其并发症的兴趣正在增加。药物的潜在功效通常在动物模型中进行测试;然而，药物递送的方法经常被忽视，并且可能由于压力而成为混淆因素。我们假设长期口胃管饲会对饮食诱导肥胖小鼠模型的肝脂肪变性和代谢综合征的发展产生负面影响。给C57 BL/6 J雄性小鼠喂食高脂肪饮食，并每天一次或两次灌胃赋形剂，持续9周。不灌胃组作为对照组。使用瘦素缺乏的ob/ob小鼠进行类似的实验，这些小鼠被喂食标准饮食4周。监测食物摄入量，确定胰岛素抵抗，并通过组织学评估脂肪变性，并通过磁共振光谱进行定量。9周后，与每天或每天两次灌胃的小鼠相比，对照C57 BL/6 J小鼠表现出显著更多的体重增加、胰岛素抵抗和肝脂肪变性。这种影响可能是由于与灌胃诱导的应激相关的摄食量减少。与此相反，瘦素缺乏的ob/ob小鼠的表型不受口胃管饲法的影响。因此，我们得出结论，口胃管饲法可能会导致应激增加，从而影响食物摄入量和饮食诱导的肥胖症在小鼠模型中的发展。在设计药物开发的动物研究时，应考虑到看似微不足道的实验室常规（如口胃灌胃）的影响。
Interest in pharmacological intervention to combat metabolic syndrome and its complications is increasing as the prevalence of obesity is reaching epidemic proportions. The potential efficacy of drugs is often tested in animal models; however, the method of drug delivery is frequently overlooked and may act as a confounder due to stress. We hypothesized that long-term orogastric gavage would negatively influence the development of hepatic steatosis and the metabolic syndrome in a murine model of diet-induced obesity. C57BL/6J male mice were fed a high fat diet and were gavaged with a vehicle once or twice daily for 9 weeks. A group without orogastric gavaging served as control. A similar experiment was performed using leptin deficient ob/ob mice that were fed a standard diet for 4 weeks. Food intake was monitored, insulin resistance determined, and steatosis was assessed by histology and quantified via magnetic resonance spectroscopy. After 9 weeks, control C57BL/6J mice exhibited significantly more weight gain, insulin resistance and hepatic steatosis, compared to mice that were gavaged daily, or twice daily. This effect was likely due to decreased food consumption associated with gavage-induced stress. In contrast, the phenotype of leptin deficient ob/ob mice was not affected by orogastric gavage. Therefore, we concluded that orogastric gavage may lead to increased stress, thereby affecting food intake and the development of diet-induced obesity in a murine model. The effects of what may seem to be trivial laboratory routines, such as orogastric gavage, should be taken into account when designing animal studies for drug development.
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影响因子：
13.5
作者：
Browning, JD;Szczepaniak, LS;Hobbs, HH
通讯作者：
Hobbs, HH
影响因子：
7.7
作者：
Marchesini, G;Brizi, M;Melchionda, N
通讯作者：
Melchionda, N
DOI：
10.1073/pnas.96.14.8283
发表时间：
1999-07-06
影响因子：
11.1
作者：
Weninger, SC;Dunn, AJ;Majzoub, JA
通讯作者：
Majzoub, JA
影响因子：
37.8
作者：
Alberti, K. G. M. M.;Eckel, Robert H.;Smith, Sidney C., Jr.
通讯作者：
Smith, Sidney C., Jr.
影响因子：
2.9
作者：
Good, T;Khan, MZ;Lynch, JW
通讯作者：
Lynch, JW