Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
Ann Nutr Metab. 2010;56(2):127-42. doi: 10.1159/000278748. Epub 2010 Feb 5.
BACKGROUND/AIMS: The metabolic syndrome (MS) has become an epidemiological problem in Western countries. We developed a diet-induced obese rat model that mimics all the symptoms of MS in humans, but whose insulin resistance, hyperphagia and hyperleptinemia are caused by nutrition rather than genetic modifications.
Spontaneously hypertensive rats (SHR) were allowed for 12 weeks to choose between a cafeteria diet (CD, 20.3 kJ/g) and standard rat chow (11.7 kJ/g). Controls received rat chow.
Body weight (BW) exceeded control levels when SHR were fed with CD. The increase in BW was attributed to enhanced energy intake. The abundance of abdominal fat as well as the plasma levels of leptin and triglycerides increased concomitant with glucose, insulin and C-peptide. This prediabetic condition was further confirmed by a markedly increased insulin response following glucose challenge and by impaired glucose utilization after insulin tolerance tests.
Increases in food intake and BW despite hyperleptinemia indicate leptin resistance following CD feeding. CD-fed SHR feature leptin and insulin resistance, hypertension and obesity, thus mimicking the situation of MS patients. As such, our model is more suitable than the genetically modified rat models used to study human MS.
背景/目的：代谢综合征（MS）在西方国家已成为一个流行病学问题。我们开发了一种饮食诱导的肥胖大鼠模型，该模型模拟了人类 MS 的所有症状，但胰岛素抵抗、多食和高瘦素血症是由营养而不是基因修饰引起的。
自发性高血压大鼠（SHR）被允许在 12 周内选择 cafeteria 饮食（CD，20.3 kJ/g）和标准大鼠饲料（11.7 kJ/g）。对照组接受大鼠饲料。
当 SHR 喂食 CD 时，体重（BW）超过对照水平。BW 的增加归因于能量摄入的增加。腹部脂肪的丰度以及血浆瘦素和甘油三酯水平的增加与葡萄糖、胰岛素和 C 肽同时升高。这种糖尿病前期状态进一步通过葡萄糖挑战后胰岛素反应明显增加和胰岛素耐量试验后葡萄糖利用受损得到证实。
尽管存在高瘦素血症，但摄食量和 BW 的增加表明 CD 喂养后存在瘦素抵抗。CD 喂养的 SHR 具有瘦素和胰岛素抵抗、高血压和肥胖，因此模拟了 MS 患者的情况。因此，我们的模型比用于研究人类 MS 的基因修饰大鼠模型更适合。
