Mühlhäusler Beverly Sara, Toop Carla, Gentili Sheridan
Food and Nutrition Research Group, Department of Food and Wine Sciences, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA, Australia.
FOODplus Research Centre, School of Agriculture, Food and Wine, The University of Adelaide, Adelaide, SA, Australia.
Methods Mol Biol. 2020;2076:43-69. doi: 10.1007/978-1-4939-9882-1_3.
In order to better understand the events that precede and precipitate the onset of type 2 diabetes (T2DM), several nutritional animal models have been developed. These models are generated by manipulating the diet of either the animal itself, or its mother during her pregnancy, and in comparison to traditional genetic and knock out models, have the advantage that they more accurately reflect the etiology of human T2DM. This chapter will discuss some of the most widely used nutritional models of T2DM: Diet-induced obesity (DIO) in adult rodents, and studies of offspring of mothers fed a low-protein, high-fat and/or high-sugar diet during pregnancy and/or lactation. Several common mechanisms have been identified through which these nutritional manipulations can lead to metabolic disease, including pancreatic beta-cell dysfunction, impaired insulin signaling in skeletal muscle, and the excess accumulation of visceral adipose tissue and consequent deposition of nonesterified fatty acids in peripheral tissues. In addition, there is an emerging concept that obesity/poor quality diets result in increased production and release of pro-inflammatory cytokines from adipose tissue leading to a state of chronic low-grade inflammation, and that this is likely to represent an important link between obesity/diet and metabolic dysfunction. The following chapter will discuss the most common nutritional models of T2DM in experimental animals, their application, and relationship to human etiology, and will highlight the important insights these models have provided into the pathogenesis of T2DM.
为了更好地理解2型糖尿病（T2DM）发病前及发病时的相关事件，人们已建立了多种营养动物模型。这些模型通过控制动物自身或其母亲孕期的饮食来构建，与传统的基因模型和基因敲除模型相比，它们的优势在于能更准确地反映人类T2DM的病因。本章将讨论一些最广泛使用的T2DM营养模型：成年啮齿动物的饮食诱导肥胖（DIO）模型，以及对孕期和/或哺乳期喂食低蛋白、高脂肪和/或高糖饮食的母亲所生后代的研究。已确定了一些常见机制，通过这些机制，这些营养干预可导致代谢疾病，包括胰腺β细胞功能障碍、骨骼肌中胰岛素信号传导受损，以及内脏脂肪组织过度积聚并随之在外周组织中沉积非酯化脂肪酸。此外，一个新出现的概念是，肥胖/不良饮食质量会导致脂肪组织产生和释放更多促炎细胞因子，从而引发慢性低度炎症状态，而这可能是肥胖/饮食与代谢功能障碍之间的重要联系。下一章将讨论实验动物中最常见的T2DM营养模型、它们的应用以及与人类病因的关系，并将突出这些模型对T2DM发病机制所提供的重要见解。
