Increased hepatocellular uptake of long chain fatty acids occurs by different mechanisms in fatty livers due to obesity or excess ethanol use, contributing to development of steatohepatitis in both settings.
Long chain fatty acids (LCFA) enter cells by both facilitated transport and diffusion, the former accounting for > or = 90%. Facilitated LCFA transport is up-regulated in adipocytes from obese rats, mice, and humans. To clarify the role of hepatocellular LCFA uptake in hepatic steatosis (fatty liver), [3H]-oleic acid (OA) uptake was studied in hepatocytes isolated from Zucker fatty(Z) and control(C) and ethanol-fed(E) Wistar rats, and demonstrated both saturable and non-saturable components, each a function of the unbound OA concentration ([OAu]). The uptake Vmax was identical in C and Z animals, but was increased 2.4-fold in E animals (p < 0.01). The non-saturable uptake rate constant did not differ between groups. Plasma LCFAs averaged 600 microM in C and E and 1,200 microM in Z animals. Total LCFA uptake averaged 1.35, 2.78 and 3.54 pmol/sec/50,000 cells in C, Z, and E animals, respectively. A 2-fold uptake increase in Z animals, in which Vmax was unaltered, entirely reflected the increased plasma LCFA concentration, whereas the 2.6-fold increase in E animals, in which plasma LCFA were not increased, resulted from up-regulation of facilitated transport. Thus, while increased hepatic LCFA uptake contributes to pathogenesis of hepatic steatosis in both obesity and excessive ethanol consumption, the mechanisms differ.
Department of Medicine, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA. pb2158@columbia.edu
Paul D
PD
Berk
Shengli
S
Zhou
Michael W
MW
Bradbury
D000818:Animals; D001693:Biological Transport, Active; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism*; D005234:Fatty Liver / Q000209:etiology / Q000378:metabolism*; D005235:Fatty Liver, Alcoholic / Q000209:etiology / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D009765:Obesity / Q000150:complications / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains
D005227:Fatty Acids