Effects of caffeine on lipoprotein lipase gene expression during the adipocyte differentiation process

In this study, the effects of caffeine on lipoprotein lipase (LPL) gene expression were investigated in the 3T3-F442A preadipocyte cell line during the adipocyte differentiation process by determining LPL enzymatic activity and its messenger RNA (mRNA) level. The results demonstrate that caffeine acts on the gene expression of LPL, an early marker of adipocyte differentiation. It has a biphasic action: it increases gene expression in terms of mRNA when it is added to preadipocytes during the early stage of differentiation, but this is accompanied by a reduction of enzymatic activity. On the other hand, when caffeine is added for long periods during differentiation and/or when it is added to mature adipocytes, it induces marked inhibition of mRNA levels, correlated with a marked reduction of secreted enzymatic activity. The inhibitory effect of caffeine on LPL mRNA level can be reproduced by theophylline, 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 that a mechanism other than inhibition of cyclic AMP hydrolysis may be involved in the action of caffeine.