BackgroundThe prevalence of Metabolic Syndrome and related chronic diseases, among them non-insulin-dependent (type 2) diabetes mellitus, are on the rise in the United States and throughout the world. Animal models that respond to environmental stressors, such as diet, are useful for investigating the outcome and development of these related diseases.ObjectiveWithin this context, growth and energy relationships were characterized in the Nile rat, an exotic African rodent, as a potential animal model for diet-induced type 2 diabetes mellitus and Metabolic Syndrome.MethodsCompiled data from several studies established the relationship between age, body weight gain (including abdominal adiposity), food and water consumption, and blood glucose levels as determinants of diabetes in male and female Nile rats. Glucose Tolerance Testing, insulin, HbA1c, blood pressure measurements and plasma lipids further characterized the diabetes in relation to criteria of the Metabolic Syndrome, while diet modification with high-fat, low-fiber or food restriction attempted to modulate the disease.ResultsThe Nile rat fed lab chow demonstrates signs of the Metabolic Syndrome that evolve into diet-induced non-insulin-dependent (type 2) diabetes mellitus characterized by hyperinsulinemia with rising blood glucose (insulin resistance), abdominal adiposity, and impaired glucose clearance that precedes increased food and water intake, as well as elevated HbA1c, marked elevation in plasma triglycerides and cholesterol, microalbuminuria, and hypertension. Males are more prone than females with rapid progression to diabetes depending on the challenge diet. In males diabetes segregated into early-onset and late-onset groups, the former related to more rapid growth and greater growth efficiency for the calories consumed. Interestingly, no correlation was found between blood glucose and body mass index (overall adiposity) in older male Nile rats in long term studies, whereas blood glucose and the perirenal fat pad, as well as liver and kidney weight, were positively related to early-onset diabetes. Rats weaned early (4-5 wks) and challenged with a high-fat Western-type diet developed diabetes faster, and body fat accumulation was more apparent, whereas food restriction curtailed it.ConclusionThe Nile rat fed typical rodent diets develops hyperinsulinemia that precedes hyperglycemia (insulin resistance) leading to diet-induced type 2 diabetes associated with hypertriglyceridemia, hypercholesterolemia, and hypertension. Dietary modulation affected growth rate (weight gain and central adiposity) to impact disease progression. This rodent model represents a novel system of gene-diet interactions affecting energy utilization that can provide insight into the prevention and treatment of the type 2 diabetes and Metabolic Syndrome.

Certain aspects of tocopherol and tocotrienol absorption, plasma transport, and tissue distribution were examined in humans and hamsters. Plasma transport differed in that tocopherols were found primarily in low density lipoprotein and high density lipoprotein in association with plasma surface components, whereas tocotrienols disappeared from plasma with chylomicron clearance. In keeping with transport by triglyceride-rich lipoproteins, tocotrienols were deposited in conjunction with triglycerides in the adipose tissue of hamsters. In hamsters, tocopherols were the only tocol readily detected in all tissues, except adipose during tocotrienol supplementation. In fasting humans, the plasma tocotrienol concentration was not significantly increased after tocotrienol supplementation, whereas the platelet concentration of delta-tocotrienol doubled. Furthermore, tocotrienol intake did not appear to modulate the plasma cholesterol concentration in normolipemic hamsters. Thus, the transport, tissue concentration, and relative biologic function of tocopherol and tocotrienol appear somewhat disparate and possibly unrelated.

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.

Three species of monkey (rhesus, cebus, and squirrel) were rotated through five purified diets containing 31% energy as various fat blends (P:S between 0.1 and 1.0) for 12-wk periods to compare the impact of specific dietary fatty acids on plasma lipids and lipoproteins. As 12:0 + 14:0 was replaced by 16:0, a significant decrease occurred in total and LDL cholesterol, whereas slight increases in total cholesterol and the LDL-HDL ratio occurred when 16:0 replaced 18:2. Hegsted and Keys regression equations provided a good fit for the observed data, but the predicted total cholesterol response was perfect (r = 0.995) for both equations when 16:0 was considered neutral. Thus, under these conditions 16:0 was less cholesterolemic than 12:0 + 14:0 and only slightly cholesterolemic compared with 18:2.