Perturbation of glycerolipid content and biosynthesis in hepatocytes of rats continuously infused with Escherichia coli endotoxin.
The effect of chronic, nonlethal endotoxemia on the endogenous content and de novo biosynthesis of glycerolipids was investigated in rat hepatocytes. Continuous E. coli endotoxin (ET) infusion for 30 hours through a subcutaneously implanted mini-pump greatly altered the composition of membrane phospholipids. Sphingomyelin (SPH) and phosphatidylserine (PS) content increased by 56% and 29%, respectively, while the content of phosphatidylcholine (PC) decreased slightly (6%) as compared with saline-infused rats. These effects contrasted with those observed in pair-fed rats (whose food intake was matched to that voluntarily consumed by ET-infused animals). Food restriction induced a great depletion of phospholipid content, mainly phosphatidylethanolamine (PE), PC, phosphatidylinositol (PI), and PS, with no changes at the level of SPH as compared with control (fed ad libitum) rats. Triacylglycerol (TG) content was greatly decreased (66%) in ET-infused rats and the magnitude of the change and the fatty acid composition followed a pattern similar to that observed in pair-fed rats. The kinetics of [2-3H]-glycerol incorporation reflected efficient utilization of the precursor for de novo biosynthesis of glycerolipids. Labeling of the intermediate metabolite phosphatidic acid (PA) peaked at an earlier time (1 min) in ET-infused, and in pair-fed rats, as compared with saline-infused and control rats (3 min) respectively, and was followed by a later peak in diacylglycerol (DG) labeling. The metabolic flux thereafter in endotoxemia reflected a redirection toward the synthesis of TG and PI, while in pair-fed animals the label went mainly to PC, concomitantly with a great reduction in the uptake of label into PI.(ABSTRACT TRUNCATED AT 250 WORDS)
Rodriguez de Turco
E B
EB
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Spitzer
J A
JA
D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D005990:Glycerol / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000032:analysis / Q000378:metabolism*
D004731:Endotoxins; D010743:Phospholipids; D014280:Triglycerides; D005990:Glycerol