Development of Glucose Intolerance in Wistar Rats Fed Low and Moderate Fat Diets Differing in Fatty Acid Profile

Background/Aims: Both dietary fat content and fatty acid composition play a role in the development of glucose intolerance and insulin resistance. In this study we investigated the effect of moderate increases in dietary fat (10-30% of fat as total calories) and associated differences in fatty acid content, on the development of metabolic perturbations in the Wistar rat. Methods: Eighteen normal male Wistar rats were randomly divided into 3 groups (n = 6 each) at weaning, and fed different diets for 10 months: D10-10% fat as energy; D20-20% fat as energy and D30-30% fat as energy ad libitum. Results: Compared with D10, rats fed D20 and D30 exhibited increased body weight from as early as 1 month of the study (p < 0.01). None of the diets resulted in hyperglycemia, but glucose intolerance developed as early as 1 month in the D20 and D30 groups (p < 0.01) following intravenous glucose tolerance test. Over time, the glucose stimulated insulin secretion rate (GSIS) became more blunted in the D20 and D30 groups, but by 10 months the D20 group regained some insulin responsiveness. D30 showed very poor GSIS at 10 months indicating glucose intolerance. Plasma omega 6 and omega 3 fatty acid profiles mostly reflected the dietary content, but the ratio of omega 6:omega 3 in plasma deteriorated over time in D30, whereas that of D10 and D20 improved. Conclusion: A moderate increase in dietary fat (20%), within the recommended nutritional range, and an unfavourable omega 6:omega 3 ratio resulted in glucose intolerance in this Wistar rat model, which was exacerbated with a further increase in dietary fat (30%).