Regulation of fatty acid transport protein and fatty acid translocase mRNA levels by endotoxin and cytokines.
The cloning of two novel fatty acid (FA) transport proteins, FA transport protein (FATP) and FA translocase (FAT), has recently been reported; however, little is known about their in vivo regulation. Endotoxin [lipopolysaccharide (LPS)], tumor necrosis factor (TNF), and interleukin-1 (IL-1) stimulate adipose tissue lipolysis and enhance hepatic lipogenesis and reesterification 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 in which 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 reesterification, LPS decreased FATP mRNA expression by 70-80% but increased FAT mRNA levels by four- to fivefold. The effects of LPS on FATP and FAT mRNA levels in liver were observed as 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 liver and adipose tissue. These results indicate that the mRNAs for both transport proteins are downregulated by LPS in tissues in which 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 toward mitochondria for oxidation, which is decreased in sepsis, whereas FAT may transport FA to cytosol for reesterification, which is enhanced in sepsis.
Memon
R A
RA
Department of Medicine, University of California, San Francisco 94143, USA.
Feingold
K R
KR
Moser
A H
AH
Fuller
J
J
Grunfeld
C
C
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D006224:Cricetinae; D005215:Fasting; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D026901:Membrane Transport Proteins; D008647:Mesocricetus; D027361:Organic Anion Transporters; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D018955:CD36 Antigens; D002352:Carrier Proteins; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha