In:
Journal of Parenteral and Enteral Nutrition, Wiley, Vol. 22, No. 5 ( 1998-09), p. 286-290
Abstract:
Background: During sepsis, lipid metabolism is shunted toward triacylglycerol synthesis and hepatic lipogenesis. A decrease in ketogenesis from free fatty acids also is observed, probably mediated by cytokines involved in host response to infection. Whether such an inhibition of ketogenesis occurs with other ketone body precursors such as ketoacids is not known. The aim of this study was to determine the effects of tumor necrosis factor alpha (TNF‐α) and interleukin 6 (IL‐6) on hepatic ketone body production from octanoic acid, a medium‐chain fatty acid, and from a‐ketoisocaproate (KIC), the ketoanalogue of leucine. Methods: The experiments were conducted in cultured hepatocytes isolated from 24‐hour‐fasted Sprague‐Dawley rats. Hepatocyte monolayers were incubated for 6 hours, with either KIC or octanoic acid (1 mmol/L), in the presence of glucagon and TNF‐α (25 μg/L) IL‐6 (15 μg/L) and/or IL‐6. Acetoacetate, β‐hydroxybutyrate, and free fatty acids were determined in culture medium by enzymatic methods and KIC was measured by high‐performance liquid chromatography. Results: KIC and octanoic acid uptake by hepatocytes was 79% and 92%, respectively, over 6 hours, and cytokines had no influence. However, TNF‐α and IL‐6 caused inhibition of ketogenesis from α‐ketoisocaproate (5.6% ± 2.3% and 4.4% ± 3.0%, respectively), and from octanoic acid (7.9% ± 2.9%, 5.7% ± 3.2%, respectively). In addition, when the two cytokines were present together in the culture medium, the inhibition was enhanced (inhibition of ketogenesis from KIC: 14.0% ± 4.8%; from octanoic acid: 11.6% ± 3.4%). Conclusions: In our experimental conditions, cytokines mediate an inhibition of ketogenesis; this process could be explained by a direct effect of cytokines on metabolic pathways of octanoic acid and KIC oran indirect effect by modification of the mitochondrial redox state. (Journal of Parenteral and Enteral Nutrition 22: 286–290, 1998)
Type of Medium:
Online Resource
ISSN:
0148-6071
,
1941-2444
DOI:
10.1177/0148607198022005286
Language:
English
Publisher:
Wiley
Publication Date:
1998
detail.hit.zdb_id:
2170060-6
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