Down-regulation of liver and heart specific fatty acid binding proteins by endotoxin and cytokines in vivo.

Abstract

Fatty acid binding proteins (FABPs) are abundantly present in tissues that actively metabolize fatty acids (FA). While their precise physiological function 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 during the host response to infection and inflammation. Previous studies have demonstrated that endotoxin or bacterial lipopolysaccharide (LPS) enhances hepatic FA synthesis and re-esterification while inhibiting FA oxidation in liver, heart and muscle. Now, we have examined the in vivo effects of LPS and cytokines on FABPs in liver (L-FABP), heart and muscle (H-FABP). Syrian hamsters were injected with LPS, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) and the mRNA and protein content for L-FABP and H-FABP were analyzed. 16 h after administration, LPS (100 microg/100 g body weight) produced a 72% decrease in L-FABP mRNA levels in liver and this effect was sustained for 24 h. LPS also produced a 41% decrease in the protein content of L-FABP in liver after 24 h of treatment. TNF-alpha and IL-1beta decreased L-FABP mRNA levels in liver by 30 and 45%, respectively. LPS decreased H-FABP mRNA levels in skeletal muscle by 60% and in heart by 65%. LPS also produced a 49% decrease in H-FABP protein content in muscle. Neither TNF-alpha nor IL-1beta had any significant effect on H-FABP mRNA expression in heart and muscle. Taken together, these results indicate that LPS decreases FABP mRNA and protein levels in liver, heart and muscle, tissues that normally utilize FA as their primary fuel, whereas the inhibitory effect of cytokines is limited to the liver. The LPS-induced decrease in L-FABP 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.

• Authors: R A Memon, N M Bass, A H Moser, J Fuller, R Appel, C Grunfeld, K R Feingold
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1440 Issue 1 Pg. 118-26 (Aug 25 1999) ISSN: 0006-3002 [Print] Netherlands
• PMID: 10477831 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carrier Proteins
• Cytokines
• Fabp1 protein, mouse
• Fatty Acid-Binding Proteins
• Lipopolysaccharides
• Myelin P2 Protein
• Neoplasm Proteins
• RNA, Messenger

Topics

• Animals
• Carrier Proteins (genetics, metabolism)
• Cricetinae
• Cytokines (pharmacology)
• Down-Regulation
• Fatty Acid-Binding Proteins
• Heart (drug effects)
• Lipopolysaccharides (pharmacology)
• Liver (drug effects, metabolism)
• Male
• Mesocricetus
• Myelin P2 Protein (genetics, metabolism)
• Myocardium (metabolism)
• Neoplasm Proteins
• RNA, Messenger (genetics, metabolism)