EFFECTS OF CAFFEINE ON LIPOPROTEIN-LIPASE GENE-EXPRESSION DURING THE ADIPOCYTE DIFFERENTIATION PROCESS

In this study, the effects of caffeine on lipoprotein lipase (LPL) gen e expression were investigated in the 3T3-F442A preadipocyte cell line during the adipocyte differentiation process by determining LPL enzym atic activity and its messenger RNA (mRNA) level. The results demonstr ate that caffeine acts on the gene expression of LPL, an early marker of adipocyte differentiation. It has a biphasic action: it increases g ene expression in terms of mRNA when it is added to preadipocytes duri ng the early stage of differentiation, but this is accompanied by a re duction of enzymatic activity. On the other hand, when caffeine is add ed for long periods during differentiation and/or when it is added to mature adipocytes, it induces marked inhibition of mRNA levels, correl ated with a marked reduction of secreted enzymatic activity. The inhib itory effect of caffeine on LPL mRNA level can be reproduced by theoph ylline, a phosphodiesterase inhibitor, and by dibutyryl cyclic AMP, a nonmetabolizable analog of cyclic AMP. However, the effect of caffeine and theophylline lasts longer than that of cyclic AMP, suggesting tha t a mechanism other than inhibition of cyclic AMP hydrolysis may be in volved in the action of caffeine.