Suppressive Effect of Tumor Necrosis Factor-.ALPHA. on Adipogenic Cell Differentiation and on Gene Expression of Hormone-Sensitive Lipase.

Abstract

Addition of human recombinant tumor necrosis factor-α (hrTNF) to confluent 3T3-L1 preadipocytes in the presence of differentiation inducers depressed both cellular differentiation into adipocytes and gene expression of hormone-sensitive lipase (HSL) without diminishing cellular viability. When hrTNF was added to 3T3-L1 cells that had differentiated into adipocytes, the cellular level of HSL mRNA was dose dependently reduced over the period of 3-12 h with a concomitant reduction in HSL activity. The reducing effect of hrTNF on the HSL mRNA level was reversible. Cycloheximide (0.1 mg/ml) suppressed the reducing effect of hrTNF, indicating that de novo protein synthesis is required for the hrTNF action. Actinomycin D (1 μg/ml) gradually reduced the HSL mRNA level in the adipocytes over 12 h without affecting the ratio of HSL mRNA to β-actin mRNA. The HSL mRNA level in primary cultures of Leydig cells was not affected by 1 nM hrTNF. In addition, interleukin-1β (100 nM) did not inhibit HSL gene expression when it was added to 3T3-L1 cells, regardless of their differentiation stage.