An animal model of spontaneous metabolic syndrome: Nile grass rat

Abstract

Metabolic syndrome (MetS) is a prevalent and complex disease, characterized by the variable coexistence of obesity, dyslipidemia, hyperinsulinaemia, and hypertension. The alarming rise in the prevalence of metabolic disorders makes it imperative to innovate preventive or therapeutic measures for MetS and its complications. However, the elucidation of the pathogenesis of MetS has been hampered by the lack of realistic models. For example, the existing animal models of MetS, i.e., genetically engineered rodents, imitate certain aspects of the disease, while lacking other important components. Defining the natural course of MetS in a spontaneous animal model of the disease would be desirable. Here, we introduce the Nile grass rat (NGR), Arvicanthis niloticus, as a novel model of MetS. Studies of over 1100 NGRs in captivity, fed normal chow, revealed that most of these animals spontaneously develop dyslipidemia (P<0.01), and hyperglycemia (P<0.01) by 1 yr of age. Further characterization showed that the diabetic rats develop liver steatosis, abdominal fat accumulation, nephropathy, atrophy of pancreatic islets of Langerhans, fatty streaks in the aorta, and hypertension (P<0.01). Diabetic NGRs in the early phase of the disease develop hyperinsulinemia, and show a strong inverse correlation between plasma adiponectin and HbA1c levels (P<0.01). These data indicate that the NGR is a valuable, spontaneous model for exploring the etiology and pathophysiology of MetS as well as its various complications.

Five stages of progressive β-cell dysfunction in the laboratory Nile rat model of type 2 diabetes

“…Previous work had established that male Nile rats exhibit many features of metabolic syndrome, including hypertension, hyperlipidemia, and hyperglycemia which proceeded to overt diabetes by approximately 6 months (Chaabo et al 2010, Noda et al 2010, Bolsinger et al 2013. FBG values above 5.6 mmol/L (100 mg/dL) were considered hyperglycemic based on clinical criteria for metabolic syndrome in humans (Alberti et al 2009).…”

“…In this study, we compared the effects of feeding a highcalorie, lowfiber (chow) diet of a type known to induce diabetes in Nile rats (Chaabo et al 2010, Noda et al 2010) with a highfiber (Hfib) control diet that more closely resembles the Nile rats' native diet. Comparison of the two groups until 12 months showed that a highfiber diet alone was effective in reducing the incidence of hyperglycemia from 83 to 0%.…”

“…Islets of Nile rats are described as degenerated (Noda et al 2010), and the concentrations of fed plasma insulin are reported to first compensate for, and then fail to respond to glucose (Chaabo et al 2010). Dietary manipulation such as caloric restriction or reduction of the energy density of food reduces diabetes incidence (Chaabo et al 2010).…”

“…However, there have been no studies investigating whether Nile rats would have similar fundamental changes in pancreatic islets as happens in humans, related to both βcell mass and glucose responsiveness. Furthermore, the Nile rat also appears to develop secondary complications of diabetes such as nephropathy (Noda et al 2010) and retinopathy (Noda et al 2014). Characterization of the model with respect to glucose metabolism would allow future studies of the pathophysiology of diabetes complications in the context of a humanlike trajectory of blood glucose and insulinlevel changes.…”

Animal Models as Tools for Translational Research: Focus on Atherosclerosis, Metabolic Syndrome and Type-II Diabetes Mellitus

“…The Nile grass rat (NGR), Arvicanthis niloticus, is a herbivorous rodent inhabiting dry savanna, woodlands, and grasslands in Africa. Noda and colleagues [138] recently showed that the NGR is a precious, spontaneous model for exploring the etiology and pathophysiology of MetS as well as its various complications.…”