Coordinate Regulation of the Expression of the Fatty Acid Transport Protein and Acyl-CoA Synthetase Genes by PPARα and PPARγ Activators

作者：Genevieve Elizabeth Martin, Kristina Schoonjans, Anne‐Marie Lefebvre, Bart Staels, Johan H. Auwerx · 发表于：Journal of Biological Chemistry · 年份：1997 · DOI：10.1074/jbc.272.45.28210 · 被引用次数：553 · 研究领域：Peroxisome Proliferator-Activated Receptors、Drug Transport and Resistance Mechanisms、Cancer, Lipids, and Metabolism

Intracellular fatty acid (FA) concentrations are in part determined by a regulated import/export system that is controlled by two key proteins, i.e. fatty acid transport protein (FATP) and acyl-CoA synthetase (ACS), which respectively facilitate the transport of FAs across the cell membrane and their esterification to prevent their efflux. The aim of this investigation was to analyze the expression pattern of FATP and ACS and to determine whether their expression was altered by agents that affect FA metabolism through the activation of peroxisome proliferator-activated receptors (PPAR) such as the fibrates and thiazolidinediones. FATP mRNA was ubiquitously expressed, with highest levels being detected in adipose tissue, heart, brain, and testis. Fibrate treatment, which is known to preferentially activate PPARalpha, induced FATP mRNA levels in rat liver and intestine and induced ACS mRNA levels in liver and kidney. The antidiabetic thiazolidinedione BRL 49653, which is a high-affinity ligand for the adipocyte-specific PPARgamma form, caused a small induction of muscle but a robust induction of adipose tissue FATP mRNA levels. BRL 49653 did not affect liver FATP and had a tendency to decrease heart FATP mRNA levels. ACS mRNA levels in general showed a similar pattern after BRL 49653 as FATP except for the muscle where ACS mRNA was induced. This regulation of FATP and ACS expression by PPAR activators was shown to be at the transcriptional level and could also be reproduced in ...