Dietary rat models in which the development of hypertriglyceridemia and that of insulin resistance are dissociated.

The consequences of chronic ingestion of a high-carbohydrate (starch + glucose [HCHO]) and high-fat (lard + corn oil [HFAT]) diet on triglyceride metabolism and insulin sensitivity were evaluated in fasted and fed rats. Compared with their HFAT counterparts, animals fed the HCHO diet displayed fasting and postprandial hypertriglyceridemia that was apparent after 3 weeks of feeding and persisted after 6 weeks. It was determined that hypertriglyceridemia was due to oversecretion of triglycerides into the circulation. During fasting triglyceride accumulation in plasma after administration of Triton WR1339 was indeed twofold higher in HCHO than in HFAT rats, whereas the global capacity for intravascular triglyceride hydrolysis, as assessed by an intravenous fat tolerance test and measurement of postheparin plasma lipoprotein and hepatic lipase activities, was comparable in both dietary cohorts. The postprandial increase in triglycerides after a high-carbohydrate meal was larger in HCHO than in HFAT rats. A fasting intravenous glucose tolerance test (IVGTT) showed that HFAT animals displayed insulin resistance after 3 weeks of feeding, which worsened after 6 weeks of treatment. Thus, the HCHO diet elicited fasting and postprandial hypertriglyceridemia without impairment of insulin sensitivity as compared with the HFAT diet, whereas the latter brought about deterioration of the sensitivity of glucose metabolism to insulin without affecting triglyceridemia. From these studies and other animal models, it is suggested that rapid delivery of fatty acids to tissues from chylomicron-derived triglycerides leads to insulin insensitivity, while fatty acids may not be available to increase endogenous production of triglycerides because they are mainly oxidized. In contrast, dietary starch/glucose increases hepatic synthesis and secretion of triglycerides that result in hypertriglyceridemia, but the deleterious effects of glucose-fatty acid competition on insulin sensitivity are prevented because endogenously derived triglycerides are catabolized more slowly and glucose is available for oxidation. The present results support the concept that coexistence of hypertriglyceridemia and resistance of glucose metabolism to insulin may be frequent but not obligatory.