K. C. Hayes

Water-Soluble Palm Fruit Extract (WSPFE) has been shown to confer anti-diabetic effects in the Nile rat (NR) (Arvicanthis niloticus). Liquid and powder WSPFE both deterred diabetes onset in NRs fed a high-carbohydrate (hiCHO) diet, but the liquid form provided better protection. In this study, NRs were fed either a hiCHO diet or the same diet added with liquid or powder WSPFE. Following feeding of the diets for 8 weeks, random blood glucose levels were measured to categorize NRs as either diabetes-resistant or diabetes-susceptible, based on a cut-off value of 75 mg/dL. Livers were then obtained for Illumina HiSeq 4000 paired end RNA-sequencing (RNA-Seq) and the data were mapped to the reference genome. Consistent with physiological and biochemical parameters, the gene expression data obtained indicated that WSPFE was associated with protection against diabetes. Among hepatic genes upregulated by WSPFE versus controls, were genes related to insulin-like growth factor binding protein, leptin receptor, and processes of hepatic metabolism maintenance, while those downregulated were related to antigen binding, immunoglobulin receptor, inflammation- and cancer-related processes. WSPFE supplementation thus helped inhibit diabetes progression in NRs by increasing insulin sensitivity and reducing both the inflammatory effects of a hiCHO diet and the related DNA-damage compensatory mechanisms contributing to liver disease progression. In addition, the genetic permissiveness of susceptible NRs to develop diabetes was potentially associated with dysregulated compensatory mechanisms involving insulin signaling and oxidative stress over time. Further studies on other NR organs associated with diabetes and its complications are warranted.

Objective: Whether dietary carbohydrate (CHO) or fat is more involved in type 2 diabetes (T2DM) induction uncomplicated by dietary fiber was addressed in a spontaneous diabetic model, the diurnal Nile rat that mimics the human condition. Methods: A total of 138 male Nile rats were fed plant-based and animal-based saturated fat where 10% energy as CHO and fat were exchanged across 5 diets keeping protein constant, from 70:10:20 to 20:60:20 as CHO:fat:protein %energy. Diabetes induction was analyzed by: 1. diet composition, i.e., CHO:fat ratio, to study the impact of diet; 2. quintiles of average caloric intake per day to study the impact of calories; 3. quintiles of diabetes severity to study the epigenetic impact on diabetes resistance. Results: High glycemic load (GLoad) was most problematic if coupled with high caloric consumption. Diabetes severity highlighted rapid growth and caloric intake as likely epigenetic factors distorting glucose metabolism. The largest weanling rats ate more, grew faster, and developed more diabetes when the dietary GLoad exceeded their gene-based metabolic capacity for glucose disposal. Diabetes risk increased for susceptible rats when energy intake exceeded 26 kcal/day and the GLoad was >175/2000 kcal of diet and when the diet provided >57% energy as CHO. Most resistant rats ate 40% energy and displaced CHO to <50% energy, thereby decreasing the number of diabetic rats and diabetes severity.

Objective: The Nile rat (Arvicanthis niloticus) is a superior model for Type-II Diabetes Mellitus (T2DM) induced by diets with a high glycemic index (GI) and glycemic load (GLoad). To better define the age and gender attributes of diabetes in early stages of progression, weanling rats were fed a high carbohydrate (hiCHO) diet for between 2 to 10 weeks. Methods: Data from four experiments compared two diabetogenic semipurified diets (Diet 133 (60:20:20, as % energy from CHO, fat, protein with a high glycemic load (GLoad) of 224 per 2000 kcal) versus Diets 73 MBS or 73 MB (70:10:20 with or without sucrose and higher GLoads of 259 or 295, respectively). An epidemiological technique was used to stratify the diabetes into quintiles of blood glucose (Q1 to Q5), after 2–10 weeks of dietary induction in 654 rats. The related metagenetic physiological growth and metabolic outcomes were related to the degree of diabetes based on fasting blood glucose (FBG), random blood glucose (RBG), and oral glucose tolerance test (OGTT) at 30 min and 60 min. Results: Experiment 1 (Diet 73MBS) demonstrated that the diabetes begins aggressively in weanlings during the first 2 weeks of a hiCHO challenge, linking genetic permissiveness to diabetes susceptibility or resistance from an early age. In Experiment 2, ninety male Nile rats fed Diet 133 (60:20:20) for 10 weeks identified two quintiles of resistant rats (Q1,Q2) that lowered their RBG between 6 weeks and 10 weeks on diet, whereas Q3–Q5 became progressively more diabetic, suggesting an ongoing struggle for control over glucose metabolism, which either stabilized or not, depending on genetic permissiveness. Experiment 3 (32 males fed 70:10:20) and Experiment 4 (30 females fed 60:20:20) lasted 8 weeks and 3 weeks respectively, for gender and time comparisons. The most telling link between a quintile rank and diabetes risk was telegraphed by energy intake (kcal/day) that established the cumulative GLoad per rat for the entire trial, which was apparent from the first week of feeding. This genetic permissiveness associated with hyperphagia across quintiles was maintained throughout the study and was mirrored in body weight gain without appreciable differences in feed efficiency. This suggests that appetite and greater growth rate linked to a fiber-free high GLoad diet were the dominant factors driving the diabetes. Male rats fed the highest GLoad diet (Diet 73MB 70:10:20, GLoad 295 per 2000 kcal for 8 weeks in Experiment 3], ate more calories and developed diabetes even more aggressively, again emphasizing the Cumulative GLoad as a primary stressor for expressing the genetic permissiveness underlying the diabetes. Conclusion: Thus, the Nile rat model, unlike other rodents but similar to humans, represents a superior model for high GLoad, low-fiber diets that induce diabetes from an early age in a manner similar to the dietary paradigm underlying T2DM in humans, most likely originating in childhood.

Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1) they are genetically or chemically modified to produce diabetes; (2) unlike humans, most require high-fat feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8–10 weeks) with high-carbohydrate (hiCHO) diets, similar to humans, and are protected by high fat (with low glycemic load) intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a striking genetic permissiveness influencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD), also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM.

With the increasing incidence of metabolic diseases, numerous bioactive phytochemicals have been proffered in the dietary prevention of these conditions. Palm fruit juice (PFJ) possesses bioactive phenolic compounds (referred to as oil palm phenolics; OPP) that may deter diabetes. The objective of the present experiments was to document the degree to which PFJ reduces diabetes symptoms in a variety of circumstances in the Nile rat (Arvicanthis niloticus), a novel model for carbohydrate-induced type 2 diabetes (type 2 diabetes mellitus; T2DM) and the metabolic syndrome. Wild-type male Nile rats (n100) were fed laboratory chow or semi-purified diabetogenic diets in five experiments lasting 4–36 weeks. PFJ was provided as a drink or mixed into the diet to provide OPP intakes from 170 to 720 mg gallic acid equivalents/kg body weight per d. Body weight and random and fasting blood glucose were assessed at different time points, and were analysed along with terminal fasting organ weights, insulin, plasma and liver lipids as measures of diabetes progression. PFJ proved to be anti-hyperglycaemic and anti-lipaemic in all experiments relative to untreated controls, delaying T2DM onset and even reversing advancing diabetes. Protection by PFJ was directly related to its OPP content, and no negative effects on energy intake or growth were observed. PFJ was effective both as a drink and mixed into the diet. Results suggest that PFJ may slow the rate of glucose absorption, reduce insulin resistance and/or enhance insulin secretion.

To replace dietary trans fatty acids (TFA), two practical options exist: revert to a natural saturated fat without cholesterol (most likely palm oil or its fractions) or move to a newer model of modified fat hardened by interesterification (IE). This review summarizes the relative risks for cardiovascular disease inherent in these options. Interestingly, both types of fat have been the subject of nutritional scrutiny for approximately the last 40 years, and both have positive and negative attributes. Only during that period has palm oil production developed to the point where it has become the major edible oil in world markets, making clinical studies of it an important objective. On the other hand, approximately 25 human studies have fed interesterified fat in one form or another over this period, some for weeks, some as a single meal. Two types of diet designs exist. Several fed a small amount of interesterified fat, usually incorporated within a margarine, and stayed below the radar of biological detection of any abnormal metabolism. A few fed interesterified fat that incorporated stearic acid, as interesterified 18:0 (IE-18:0), even comparing it to trans fat and saturated fat, as a major part of total daily calories to assess its metabolic impact per se. These latter 5 to 6 studies clearly reveal negative biological effects on lipoproteins, blood glucose, insulin, immune function, or liver enzymes when relatively high intake of IE-18:0 or palmitic acid (IE-16:0) were fed in fats with sn2–saturated fatty acids. High intake of 18:0 in natural fats can depress total lipoproteins, while IE-18:0 and IE-16:0 at high levels adversely affect lipoprotein metabolism. Still other studies have supplied interesterified fat as a single meal or fed such fat daily only in a single snack, as opposed to incorporating the fat into the entire fat pool consumed at all meals in association with most foods (which is the more physiological approach and more apt to elicit effects). Even in meal studies, IE-18:0 typically delayed fat absorption postprandially, indicating its effect on fat metabolism originating, in part, in the intestine. Mainly 2 saturated fatty acids (18:0 or 16:0) have been interesterified to harden oils, using the 16:0 from fully hydrogenated palm oil or 18:0 from fully hydrogenated soybean oil as the source material. It is not clear that IE-16:0 is as problematic as IE-18:0, but IE-16:0 has been studied less. Levels between 8% energy (%E) and 12%E from 18:0 as interesterified fat (the typical diet provides about 2%E–4%E as 18:0 from natural fats) show the most effect. Detection of adverse effects would seem to start around 7%E–8%E as IE-18:0, but one can assume that effects are initiated, even if undetected, at a lower intake, similar to the situation with TFA. Thus, although an intake of 1%E to 4%E from IE-18:0 does not appear to influence lipoproteins, it is not necessarily the only system affected. The negative effects of IE-18:0 may be alleviated or masked by dilution with other fats, especially by adding 18:2-rich polyunsaturated oils to the diet. This is similar to the trans fat story, i.e., if a limited intake of TFA is heavily diluted with other oils, the consumption of TFA fails to be detected as an adverse effect. Accordingly, more research is warranted to determine the appropriateness of interesterified fat consumption, particularly before it becomes insidiously embedded in the food supply similar to TFA and intake levels are achieved that compromise long-term health.

(2010). Fatty Acid Expert Roundtable: Key Statements about Fatty Acids. Journal of the American College of Nutrition: Vol. 29, No. sup3, pp. 285S-288S.

Background: The 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.Objective: Within 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.Methods: Compiled 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.Results: The 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.Conclusion: The 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.