PANTETHINE STIMULATES LIPOLYSIS IN ADIPOSE-TISSUE AND INHIBITS CHOLESTEROL AND FATTY-ACID SYNTHESIS IN LIVER AND INTESTINAL-MUCOSA IN THE NORMOLIPIDEMIC RAT

In vitro effects of pantethine on adipose tissue lipolysis and on both hepatic and intestinal cholesterol and fatty acid synthesis in normol ipidemic rats are determined and related to their respective in vivo h ypolipidemic effects after acute oral administration. At 3, 5, 7 and 2 4 h after a single high dose of pantethine to rats, free fatty acids ( FFA), cholesterol and triglycerides levels decreased whereas plasma gl ycerol increased, the effect becoming significant at 7 h. The release of glycerol and FFA by epididymal fat pad pieces from rats was measure d in Krebs Ringer bicarbonate-albumin buffer supplemented or not with epinephrine and several concentrations of pantethine (0,10(-5), 10(-4) , or 10(-3) M), and it turned out to be enhanced as pantethine concent ration increased. Besides, when glucose was present in the medium; thi s drug lowered fatty acid re-esterification in a dose-dependent manner , the effect being specially evident in the presence of epinephrine. I n vitro synthesis of both cholesterol and fatty acids by slices of liv er or intestinal epithelial cells was depressed as the concentration o f pantethine increased in the medium. Thus, an inhibition of both chol esterolgenesis and lipogenesis seems to contribute to the hypocholeste rolemic and hypotriglyceridemic effects of pantethine. On the other ha nd, the stimulation of lipolysis and the inhibition of fatty acid re-e sterification on adipose tissue caused by pantethine must be counterac ted by a high fatty acid oxidation in the liver which would explain th e decrease in FFA and the increase in glycerol levels detected in the plasma of the pantethine-treated animals. (C) 1998 Elsevier Science B. V. All rights reserved.