The regulation and initial functional characterization of long -chain fatty acid transport.

摘要

Long-chain, non-esterified fatty acids (LCFA) are major components of the dietary fatty acid intake and serve as critical building blocks for the synthesis of numerous fatty acid derived signaling molecules, lipids and triglycerides that are essential for organ development and function. Based on converging scientific and medical evidence, it is postulated that fatty acid translocase (FAT/CD36) could be the major lipid transport mediator that provides lipids and fatty acids for metabolic energy. Data also suggested that peroxisome proliferator-activated receptors (PPARs) regulate the gene transcription level of FAT/CD36 with the aid of 9-cis-retinoic acid receptors (RXRs). The focus of the current research is to elucidate the physiological and functional relevance of FAT/CD36 and its regulators in the rat and human placentas and GI tracts. The expression of PPAR and RXR isoforms were investigated in the rat and human placentas. The spatial patterns of expression of fatty acid transporters, PPAR and RXR isoforms were also characterized in the rat and human GI tracts. In addition, several in vitro mammalian cell lines that stably express FAT/CD36 to study its cell specific role in the LCFA transport were established. Finally, the LCFA uptake studies were carried out and compared between these cell lines. The results exhibited that those fatty acid transporters, PPARs and RXRs were widely expressed in the body, suggesting the coordination effects of these proteins on lipid homeostasis. Furthermore, FAT/CD36-transfected cell lines had increased LCFA uptake and the treatment of cells with anion transport inhibitor blocked the LCFA uptake. These studies will provide a foundation for further investigation of the affinity of FAT/CD36 for physiologically endogenous substrates and LCFAs, and may provide an assessment of FAT/CD36 as a potential target with respect to the design of therapeutic agents.