High-Fat High-Energy Feeding Impairs Fasting Glucose and Increases Fasting Insulin Levels in the Göttingen Minipig

: High-fat dietand obesityare known to be of major importance for development of type 2 diabetes in humans. High-fat feeding can induce syndromes of glucose intolerance and/or insulin resistance in several species, and the Gottingen minipigmight be a useful model for studying the effect of dietary high-fat intake and obesity on glucose homeostasis and the susceptibility to diabetes. The present study was designed as a pilot study to investigate the effects of obesity caused by high-fat high-energy feeding on oral and intravenous glucose tolerance. Male Gottingen minipigswere fed a control diet (CD) or a high-fat high-energy diet (HFD) for 3 months. Body weight (32.6 ± 2.4 kg vs. 24.9 ± 0.5 kg, p < 0.001) and total (13.2 ± 3.2% vs. 6.1 ± 0.5%, p= 0.002) and truncal (11.0 ± 3.9% vs. 1.8 ± 1.1%, p= 0.001) fat percent were increased significantly, whereas relative lean body masswas decreased (84.8 ± 3.3% vs. 91.9 ± 0.5%, p= 0.002) in the HFD group compared to CD. Fasting plasma glucose (4.3 ± 0.4 mM vs. 3.6 ± 0.3 mM, p= 0.023) and insulin (80 ± 23 pM vs. 23 ± 21 pM, p= 0.012) were increased in the HFD group compared to CD, but oral glucose tolerance was not significantly changed. Insulin responses to intravenous glucose were increased (6741 ± 2538 vs. 3938 ± 771 pM 3 min, p= 0.050), while glucose clearance was not changed by HFD vs. CD, thus indicating insulin resistance. In conclusion, changes in body weight and composition, resulting in minor abnormalities in glucose tolerance and insulin sensitivity, characterized by slight hyperglycemia and compensatory hyperinsulinemia, can be induced in the male Gottingen minipigby high-fat high-energy feeding for 3 months. This approach seems to be an interesting and promising method for establishment of a nonrodent model of insulin resistance or type 2 diabetes.