👤 F J Soriguer

The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r = -0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state. Show less

The apolipoprotein AI-CIII-AIV cluster has been associated with the response to a urate-lowering diet, and polymorphisms in the apolipoprotein CIII gene have been associated with hyperuricemia and hypertriglyceridemia. We assessed the influence of polymorphisms in the apolipoprotein AI-CIII-AIV cluster on the response to a urate-lowering diet in patients with hyperuricemia. A urate-lowering diet was followed for 2 weeks by 64 men with hyperuricemia. Plasma concentrations of triglycerides, cholesterol, glucose, and uric acid, and the uric acid clearance and 24-hour uric acid urinary excretory fraction were measured before and after the diet. The data were analyzed in association with the polymorphisms of the apolipoprotein AI-CIII-AIV gene cluster. After the urate-lowering diet, the plasma levels of triglycerides, cholesterol, glucose, and uric acid and 24-hour uric acid excretion all fell significantly. Paired sample ANOVA showed that the decrease was mainly due to the diet, except for the plasma triglycerides, which were influenced by allele X2 of the XmnI polymorphism of the apolipoprotein AI gene. The response of the biological variables to a urate-lowering diet was mainly influenced by diet. Changes in triglycerides were also influenced by the apolipoprotein AI XmnI polymorphism (p = 0.04), suggesting a gene-diet interaction (p = 0.03). Show less

Studies have shown that hyperuricaemia is independently related to the insulin resistance syndrome and that polymorphisms of the apolipoprotein AI-CIII-AIV cluster are also related to insulin resistance. To study the prevalence of polymorphisms of the apolipoprotein AI-CIII-AIV cluster in persons with gout and to determine whether these polymorphisms contribute to the pathophysiology of gout or to altered lipid concentrations. Plasma cholesterol, triglycerides, uric acid, VLDL, LDL, IDL, and HDL triglycerides, cholesterol, and the renal excretion of uric acid were measured in 68 patients with gout with gout and 165 healthy subjects. Polymorphisms were studied by amplification and RFLP in all subjects, using XmnI and MspI in the apolipoprotein AI gene and SstI in the apolipoprotein CIII gene. The A allele at position -75 bp in the apolipoprotein AI gene was more common in patients with gout than in controls (p = 0.01). Levels of cholesterol, triglycerides, uric acid, basal glycaemia, and HDL cholesterol were higher in the patients (p<0.001). In the patients there was also an interaction between mutations at the two polymorphic loci studied in the apolipoprotein AI gene (p = 0.04). An absence of the mutation at position -75 bp of the apolipoprotein AI gene resulted in increased plasma triglyceride levels. Gouty patients have an altered allelic distribution in the apolipoprotein AI-CIII-AIV cluster, which could lead to changes in levels of lipoproteins. This is not caused by a single mutation but rather by a combination of different mutations. Show less