Down-regulation of liver and heart specific fatty acid binding proteins byendotoxin and cytokines in vivo

Fatty acid binding proteins (FABPs) are abundantly present in tissues that actively metabolize fatty acids (FA). While their precise physiological fun ction is not known, FABPs have been shown to play a role in the uptake and/ or utilization of FA within the cell. FA metabolism is markedly altered dur ing the host response to infection and inflammation. Previous studies have demonstrated that endotoxin or bacterial lipopolysaccharide (LPS) enhances hepatic FA synthesis and reesterification while inhibiting FA oxidation in liver, heart and muscle. Now, we have examined the in vivo effects of LPS a nd cytokines on FABPs in liver (L-FABP), heart and muscle (H-FABP). Syrian hamsters were injected with LPS, tumor necrosis factor-alpha (TNF-alpha) an d interleukin-1 beta (IL-1 beta) and the mRNA and protein content for L-FAB P and H-FABP were analyzed. 16 h after administration, LPS (100 mu g/100 g body weight) produced a 72% decrease in L-FABP mRNA levels in liver and thi s effect was sustained for 34 h. LPS also produced a 41% decrease in the pr otein content of L-FABP in liver after 24 h of treatment. TNF-alpha and IL- 1 beta decreased L-FABP mRNA levels in liver by 30 and 45%, respectively. L PS decreased H-FABP mRNA levels in skeletal muscle by 60% and in heart by 6 5%. LPS also produced a 49% decrease in H-FABP protein content in muscle. N either TNF-alpha nor IL-1 beta had any significant effect on H-FABP mRNA ex pression in heart and muscle. Taken together, these results indicate that L PS decreases FABP mRNA and protein levels in liver, heart and muscle, tissu es that normally utilize FA as their primary fuel, whereas the inhibitory e ffect of cytokines is limited to the liver. The LPS-induced decrease in L-F ABP and H-FABP may be an additional mechanism contributing to the decrease in FA oxidation that is associated with the host response to infection and inflammation. (C) 1999 Elsevier Science B.V. All rights reserved.