Diane Abdoulaye, Pierce W David, Kelly Sandra E, Sokolik Sharon, Borthwick Faye, Jacome-Sosa Miriam, Mangat Rabban, Pradillo Jesus Miguel, Allan Stuart McRae, Ruth Megan R, Field Catherine J, Hutcheson Rebecca, Rocic Petra, Russell James C, Vine Donna F, Proctor Spencer D
Metabolic and Cardiovascular Diseases Laboratory, Division of Human Nutrition, Alberta Diabetes and Mazakowski Heart Institutes, University of Alberta , Edmonton, AB , Canada.
Department of Sociology, University of Alberta , Edmonton, AB , Canada.
Front Nutr. 2016 Oct 10;3:44. doi: 10.3389/fnut.2016.00044. eCollection 2016.
Obesity and its metabolic complications have emerged as the epidemic of the new millennia. The use of obese rodent models continues to be a productive component of efforts to understand the concomitant metabolic complications of this disease. In 1978, the rat model was developed with an autosomal recessive corpulent () trait resulting from a premature stop codon in the extracellular domain of the leptin receptor. Rats that are heterozygous for the trait are lean-prone, while those that are homozygous () spontaneously display the pathophysiology of obesity as well as a metabolic syndrome (MetS)-like phenotype. Over the years, there have been formidable scientific contributions that have originated from this rat model, much of which has been reviewed extensively up to 2008. The premise of these earlier studies focused on characterizing the pathophysiology of MetS-like phenotype that was spontaneously apparent in this model. The purpose of this review is to highlight areas of recent advancement made possible by this model including; emerging appreciation of the "thrifty gene" hypothesis in the context of obesity, the concept of how chronic inflammation may drive obesogenesis, the impact of acute forms of inflammation to the brain and periphery during chronic obesity, the role of dysfunctional insulin metabolism on lipid metabolism and vascular damage, and the mechanistic basis for altered vascular function as well as novel parallels between the human condition and the female rat as a model for polycystic ovary disease (PCOS).
肥胖及其代谢并发症已成为新千年的流行病。肥胖啮齿动物模型的使用仍然是了解这种疾病伴随的代谢并发症的有效组成部分。1978年，开发了一种大鼠模型，其具有常染色体隐性肥胖（）特征，这是由瘦素受体细胞外结构域中的过早终止密码子导致的。具有该特征杂合子的大鼠倾向于瘦，而纯合子（）大鼠则自发地表现出肥胖的病理生理学以及类似代谢综合征（MetS）的表型。多年来，这个大鼠模型做出了巨大的科学贡献，其中大部分在2008年之前已经得到了广泛的综述。这些早期研究的前提集中在表征该模型中自发出现的类似MetS表型的病理生理学。本综述的目的是强调该模型最近取得进展的领域，包括：在肥胖背景下对“节俭基因”假说的新认识、慢性炎症如何驱动肥胖发生的概念、慢性肥胖期间急性炎症形式对大脑和外周的影响、胰岛素代谢功能障碍对脂质代谢和血管损伤的作用、血管功能改变的机制基础以及人类状况与雌性大鼠作为多囊卵巢疾病（PCOS）模型之间的新平行关系。
