Regulation of lipoprotein lipase mRNA content in 3T3-L1 cells by tumour necrosis factor

Abstract

Tumour necrosis factor (TNF) was previously shown to suppress lipoprotein lipase (LPL) synthesis and activity in 3T3-L1 adipocytes. The present study examined the effect of TNF on amounts of mRNA for LPL in 3T3-L1 cells. Northern-blot analysis of polyadenylated RNA using a cDNA probe to guinea-pig LPL identified two predominant species of LPL message, 3.7 and 3.9 kilobases in size. The steady-state amounts of these mRNAs increased 10-fold upon expression of the adipocyte phenotype. A single dose of 1.5 nM-TNF decreased LPL mRNA by approx. 60% in 17 h with a corresponding decrease in LPL activity, an effect that was reversed 48 h after exposure to TNF. The results demonstrate that TNF reversibly down-regulates LPL mRNA in fully differentiated 3T3-L1 adipocytes. Cells induced to differentiate in the presence of 1.5 nM-TNF exhibited a delayed time course for development of the adipocyte phenotype, as judged by attenuation of the normal increase in LPL mRNA that occurs with differentiation.