Differential regulation of fatty acid transport protein and fatty
acid translocase mrna levels by endotoxin and cytokines.
Memon, Riaz A., Kenneth R. Feingold, Arthur H. Moser, John Fuller, and
Carl Grunfeld.
Department of Medicine, University of California San Francisco and
Metabolism Section, Medical Service, Department of Veterans Affairs
Medical Center, San Francisco, CA 94121
APStracts 4:0227E, 1997.
The cloning of two novel fatty acid (FA) transport proteins, FA
transport protein (FATP) and FA translocase (FAT), have recently been
reported, however, little is known about their in vivo regulation.
Endotoxin (LPS), tumor necrosis factor (TNF) and interleukin-1 (IL-1)
stimulate adipose tissue lipolysis, enhance hepatic lipogenesis and
re-esterification while suppressing FA oxidation in multiple tissues.
Hence, in this study we examined their effects on FATP and FAT mRNA
levels in Syrian hamsters. Our results demonstrate that LPS decreased
FATP and FAT mRNA expression in adipose tissue, heart, skeletal
muscle, brain, spleen and kidney, tissues where FA uptake and/or
oxidation is decreased during sepsis. In the liver, where FA
oxidation is decreased during sepsis but the uptake of peripherally
derived FA is increased to support re-esterifiation, LPS decreased
FATP mRNA expression by 70-80% but increased FAT mRNA levels by 4-5
fold. The effects of LPS on FATP and FAT mRNA levels in liver were
observed as early as 4 hours after administration and were maximal by
16 hours. TNF and IL-1 mimicked the effect of LPS on FATP and FAT
mRNA levels in both liver and adipose tissue. These results indicate
that the mRNAs for both transport proteins are down-regulated by LPS
in tissues where FA uptake and/or oxidation are decreased during
sepsis. On the other hand, differential regulation of FATP and FAT
mRNA in liver raises the possibility that these proteins may be
involved in transporting FA to different locations inside the cell.
FATP may transport FA towards mitochondria for oxidation which is
decreased in sepsis whereas FAT may transport FA to cytosol for re
-esterification which is enhanced in sepsis.
Received 3 July 1997; accepted in final form 9 October 1997.
APS Manuscript Number E310-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 29 October 1997