title: Inhibition of hepatic ketogenesis by tumor necrosis factor-alpha in rats.
abstract: Tumor necrosis factor-alpha (TNF-alpha) stimulates hepatic lipogenesis. Therefore, it could play a role in the control of ketogenesis. To test this hypothesis, we measured simultaneously free fatty acids (FFA; [1-13C]palmitate) and ketone body (KB; [3,4-13C2]acetoacetate) kinetics, before and after intraperitoneal injection of saline or TNF-alpha, in postabsorptive rats or rats starved for 24 h. In both groups of rats, TNF-alpha injection did not modify insulinemia and induced a moderate increase of FFA concentrations and appearance rates (P < 0.05). Despite increased FFA availability, ketogenesis was impaired after TNF-alpha injection, as shown by lower KB concentrations and appearance rates; this effect was more important in postabsorptive than in starved rats. The percentage of FFA flux used for ketogenesis was decreased by TNF-alpha in the postabsorptive group (P < 0.05) and starved (P < 0.05) rats. In both groups, maximal liver acetyl-coenzyme A carboxylase activity and estimated phosphorylation state were not modified by TNF-alpha injection, but hepatic concentrations of citrate were increased (P < 0.05). This increased citrate level could be related to a mobilization of glucose stored as glycogen since liver glycogen was decreased by TNF-alpha injection (P < 0.05). In conclusion, TNF-alpha injection in rats decreased hepatic ketogenesis. This action could be related to an increased mobilization and utilization of carbohydrate stores.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U.197 Faculté A. Carrel, Lyon, France.
authors.forename: M
authors.initials: M
authors.lastname: Beylot
authors.forename: H
authors.initials: H
authors.lastname: Vidal
authors.forename: G
authors.initials: G
authors.lastname: Mithieux
authors.forename: M
authors.initials: M
authors.lastname: Odeon
authors.forename: C
authors.initials: C
authors.lastname: Martin
mesh_terms: D000042:Absorption; D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007657:Ketone Bodies / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013217:Starvation / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D014409:Tumor Necrosis Factor-alpha; D006003:Glycogen