Intracytoplasmic triglyceride accumulation produced by dexamethasone in adult rat hepatocytes cultivated on 3T3 cells.
Glucocorticoids, such as hydrocortisone (HC) and dexamethasone (DEX), when administered to rats, induce lipid accumulation within hepatocytes (fatty liver). To investigate whether glucocorticoids can produce triglyceride (TG) accumulation as they do in vivo and the involved mechanisms, we have used primary cultures of rat hepatocytes which synthesized and secrete triglycerides into the culture medium. Hepatocytes cultivated on a feeder layer of lethally treated 3T3 cells were exposed for 2 weeks to micromolar concentrations of DEX. This glucocorticoid caused morphological alterations and cells accumulated lipid droplets in their cytoplasm; the TG content increased up to 6-fold in a concentration- and time-dependent manner. The removal of [14C]acetic or [14C]oleic acid from the culture medium was not altered in the cultures treated with 50 micrograms/ml DEX but the incorporation of [14C]acetic and [14C]oleic acid into TG in these cultures was about 13-fold and 60% higher than in non-treated cells, respectively. On the other hand, hepatocytes treated with 50 micrograms/ml DEX for 2 weeks showed a 16-fold decrease in TG release and 40% inhibition in protein export, whereas synthesis of total cellular proteins was not altered. Our results show that corticosteroids, such as DEX, caused lipid accumulation in liver cells through an increased synthesis and/or esterification of fatty acids, but mostly through a decrease in the secretion of TG.
Mendoza-Figueroa
T
T
Department of Pharmacology and Toxicology, Centro de Investigacion y de Estudios Avanzados del IPN, Mexico City, D.F.
Hernandez
A
A
De Lourdes Lopez
M
M
Kuri-Harcuch
W
W
D000818:Animals; D002478:Cells, Cultured; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism*
D014280:Triglycerides; D003907:Dexamethasone