Intestinal absorption and chylomicron resecretion of dietary cholesterol in obese insulin resistant dogs

Abstract

We aimed to investigate the effects of insulin resistance on intestinal absorption and chylomicron resecretion of cholesterol in dogs. Six healthy beagle dogs were overfed for 25 weeks to induce obesity and insulin resistance. Percent cholesterol absorption was assessed with the dual isotope method. [3,4-13C2]-cholesterol was given orally to study tracer enrichment in chylomicron during an 8-hour postprandial state. Lipids and microsomal triglyceride transfer protein (MTP) activity in liver and intestine were also measured. Insulin resistant dogs showed higher total cholesterol, triglycerides (TG) and free fatty acids levels (FFA) in both fasting and postprandial states (p<0.05). Percent cholesterol absorption was lower (86.5 ± 5.1 vs 68.9 ± 1.6 %, p<0.05). Postprandial chylomicron cholesteryl esters area under the curve (AUC) was higher (2.2 ± 0.3 vs 7.8 ± 0.5, p<0.05), as well as chylomicron triglycerides AUC (4.8 ± 0.5 vs 6.7 ± 0.8, p<0.05). Chylomicron [3,4-13C2]-free cholesterol AUC was lower in insulin resistant dogs (0.164 ± 0.023 vs 0.122 ± 0.017, p<0.05) but chylomicron [3,4-13C2]-cholesteryl esters AUC did not change. Total cholesterol, TG, FFA levels and MTP activity were all higher (p<0.05) in liver. There was no change in duodenum. Although insulin resistant dogs show lower intestinal cholesterol absorption and reduced chylomicron free cholesterol resecretion, this animal model is characterized by both fasting and postprandial dyslipidemia. This study was supported by grants from the National Veterinary School of Nantes and INSERM.