Fibrates are peroxisome proliferator-activated receptor-alpha (PPARalpha) ligands in widespread clinical use to lower plasma triglyceride levels. We investigated the effect of fenofibrate and clofibrate on ion transport in mouse intestine and in human T84 colonic adenocarcinoma cells through the use of short-circuit current (I(sc)) and ion flux analysis. In mice, oral administration of fenofibr...

The influence of different plasma triglyceride concentrations on the heterogeneity of low density lipoprotein (LDL) and on the susceptibility of LDL to copper oxidation was investigated. By density gradient ultracentrifugation, LDL subfractions were isolated from the plasma of 10 normolipidemic control subjects and 12 hypertriglyceridemic patients both before and after clofibrate treatment. In ...

Splanchnic metabolism of triglycerides and other major substrates was studied in the postabsorptive state in normotriglyceridemic and hypertriglyceridemic human subjects who received (1/2) g of clofibrate four times daily for 3 wk. Transport in blood plasma of triglycerides produced in the splanchnic region was quantified by three methods: (a) measurement of the transsplanchnic gradient of (14)...

The pathogenesis of NASH is unknown but may relate to excessive accumulation of lipids in the liver. Steatotic livers secondary to alcohol abuse or associated with type Il diabetes mellitus contain predominantly triglycerides and to a lesser extent cholesterol esters. Elevated hepatic free fatty acids, products of triglyceride hydrolysis, have been identified in fatty liver of pregnancy, alcoho...

pidemic drug clofibrate (ethyl-a-p-chlorophenoxyisobutyr ate) in lowering serum lipid levels in experimental animals (49) but it did not enter into clinical trials, possibly due to suspected hepatotoxicity in experimental animals. Previous work by Reddy and Knishnakantha (31) showed that Wy 14,643 caused a significant hepatomegaly and produced a marked increase in the hepatic peroxisome populat...

BACKGROUND: Peroxisome proliferators are considered rodent carcinogens that are putative human non-carcinogens based on the presumed absence of direct genetic toxicity in rodent and human cells and the resistance of human cells to the induction of peroxisomes by peroxisome proliferators. The highly sensitive lacZ plasmid-based transgenic mouse mutation assay was employed to investigate the muta...