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非酒精性脂肪性肝炎的肥胖饮食性小鼠模型。

An Obesogenic Dietary Mouse Model of Nonalcoholic Steatohepatitis.

机构信息

Bioscience Metabolism, Research and Early Development, Cardiovascular, Renal and Metabolic (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

The Lundberg Laboratory for Diabetes Research, University of Gothenburg, Gothenburg, Sweden.

出版信息

Methods Mol Biol. 2020;2164:121-127. doi: 10.1007/978-1-0716-0704-6_13.

Abstract

Nonalcoholic steatohepatitis (NASH) is a severe form of nonalcoholic fatty liver disease (NAFLD), characterized by steatosis (fat within the liver), inflammation, and fibrosis, which may progress to cirrhosis and hepatocellular carcinoma. Despite the high prevalence, there are currently no approved NASH drug treatments, which urges a faster development of new therapies to address this high unmet medical need. Drug development is facilitated by having reliable and translatable preclinical NASH models. Obesogenic dietary models recapitulate better the natural progression of NASH, with overnutrition and sedentary lifestyle being the main causes. Here we describe the use of a modified version of a diet-induced NASH model, known as the Amylin NASH diet model (AMLN-diet), particularly in the leptin-deficient Lep/Lep (ob/ob) mice.

摘要

非酒精性脂肪性肝炎(NASH)是一种严重的非酒精性脂肪性肝病(NAFLD),其特征为脂肪变性(肝脏内的脂肪)、炎症和纤维化,可能进展为肝硬化和肝细胞癌。尽管患病率很高,但目前尚无批准的 NASH 药物治疗方法,这迫切需要更快地开发新的治疗方法来满足这一未满足的高医疗需求。药物开发得益于具有可靠和可转化的临床前 NASH 模型。致肥胖饮食模型更好地再现了 NASH 的自然进展,营养过剩和久坐不动的生活方式是主要原因。在这里,我们描述了一种改良的饮食诱导 NASH 模型的使用,称为胰岛淀粉样多肽 NASH 饮食模型(AMLN-diet),特别是在瘦素缺乏的 Lep/Lep(ob/ob)小鼠中。

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