REGULATION OF FATTY-ACID TRANSPORT PROTEIN AND FATTY-ACID TRANSLOCASEMESSENGER-RNA LEVELS BY ENDOTOXIN AND CYTOKINES

The cloning of two novel fatty acid (FA) transport proteins, FA transp ort protein (FATP) and FA translocase (FAT), has recently been reporte d; however, little is known about their in vivo regulation. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleuk in-1 (IL-1) stimulate adipose tissue lipolysis and enhance hepatic lip ogenesis and reesterification while suppressing FA oxidation in multip le 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, skele tal muscle, brain, spleen, and kidney tissues in which FA uptake and/o r oxidation is decreased during sepsis. In the liver, where FA oxidati on is decreased during sepsis but the uptake of peripherally derived F A is increased to support reesterifiation, LPS decreased FATP mRNA exp ression by 70-80% but increased FAT mRNA levels by four-to fivefold. T he effects of LPS on FATP and FAT mRNA levels in liver were observed a s early as 4 h after administration and were maximal by 16 h. TNF and IL-1 mimicked the effect of LPS on FATP and FAT mRNA levels in both li ver and adipose tissue. These results indicate that the mRNAs for both transport proteins are downregulated by LPS in tissues in which FA up take and/or oxidation are decreased during sepsis. On the other hand, differential regulation of FATP and FAT mRNA in liver raises the possi bility that these proteins may be involved in transporting FA to diffe rent locations inside the cell. FATP may transport FA toward mitochond ria for oxidation, which is decreased in sepsis, whereas FAT may trans port FA to cytosol for reesterification, which is enhanced in sepsis.