AJP - Endocrinology and Metabolism, Vol 263, Issue 5 E897-E902, Copyright © 1992 by American Physiological Society
Inhibition of hepatic ketogenesis by tumor necrosis factor-alpha in rats
M. Beylot, H. Vidal, G. Mithieux, M. Odeon and C. Martin
Institut National de la Sante et de la Recherche Medicale U.197 Faculte A. Carrel, Lyon, France.
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.
