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Effect of sepsis-related cytokines on lipid synthesis by isolated human hepatocytes
J Arias-Díaz1, E Vara, M Gómez
1Department of Surgery, U. Complutense de Madrid, Ciudad Universitaria, Spain.
Objective:
To investigate the effect of tumour necrosis factor-alpha (TNF-alpha) and other sepsis related cytokines on the synthesis of several lipid fractions by human hepatocytes.
Design:
Laboratory study.
Setting:
University departments of surgery and biochemistry.
Material:
Livers from eight donors of other organs.
Main Outcome Measures:
Effect of TNF-alpha, interleukin-1 (IL-1), and interleukin-6 (IL-6) on the synthesis of triacylglycerol and phospholipids by freshly isolated human hepatocytes.
Results:
All three cytokines, particularly TNF-alpha, inhibited the incorporation of D-glucose uniformly labelled with 14C (D-(U-14C) glucose) into phosphatidylcholine. The incorporation of D-(U-14C) glucose into triacylglycerol and free fatty acids was significantly stimulated by TNF-alpha and IL-1, but not by IL-6. When palmitate uniformly labelled with 14C was used as the radiolabelled precursor, TNF-alpha stimulated the synthesis of both triacylglycerol and phosphatidylcholine, neither of which was affected by IL-1 or IL-6.
Conclusion:
Changes that are induced by cytokines in lipid synthesis by hepatocytes can contribute to the impairment of lipid metabolism seen in septic patients. TNF-alpha seemed to have more effect than the other two cytokines.