title: Effect of different sepsis-related cytokines on lipid synthesis by isolated hepatocytes.
abstract: Cytokines seem to play an important role in the metabolic disturbances that are commonly associated with sepsis. In this study, we analyzed the effect of tumor necrosis factor, interleukin-1 and interleukin-6, as well as that of tumor necrosis factor in combination with interleukin-1 or interleukin-6, both on free fatty acids and on phospholipid synthesis by isolated rat hepatocytes. All three cytokines and combinations caused inhibited D-[U-14C]glucose incorporation into phosphatidylcholine (tumor necrosis factor = 6.39 +/- 1.13 pmol/microgram protein vs. control = 12.90 +/- 0.98 pmol/microgram protein, n = 7; p < 0.001). However, when [U-14C]palmitate was used as radioactive precursor, tumor necrosis factor, either alone or in the presence of the other cytokines, stimulated phosphatidylcholine synthesis. D-[U-14C]glucose incorporation into free fatty acids and triacylglycerol was also significantly stimulated, whereas phosphatidylinositol labeling was found inhibited by the assayed cytokines. Our results demonstrate an effect of sepsis-related cytokines, more evident for tumor necrosis factor, on hepatocyte lipid synthesis either from glucose or palmitate. Also, the findings support the hypothesis that cytokine-induced changes in hepatocyte lipid synthesis can contribute to the impairment in lipidic metabolism seen in patients with sepsis.
authors.affiliation: Department of Biochemistry, School of Medicine, Complutense University, Madrid, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Vara
authors.forename: J
authors.initials: J
authors.lastname: Arias-Díaz
authors.forename: J
authors.initials: J
authors.lastname: Torres-Melero
authors.forename: C
authors.initials: C
authors.lastname: García
authors.forename: J M
authors.initials: JM
authors.lastname: Rodríguez
authors.forename: J L
authors.initials: JL
authors.lastname: Balibrea
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis; D005947:Glucose / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology; D015850:Interleukin-6 / Q000494:pharmacology / Q000502:physiology; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D010168:Palmitates / Q000378:metabolism; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism*; D014280:Triglycerides / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology
chemical_list: D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D007375:Interleukin-1; D015850:Interleukin-6; D008055:Lipids; D010168:Palmitates; D010713:Phosphatidylcholines; D010716:Phosphatidylinositols; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose