Expression of hepatic lipase (HL) in the liver is reduced during prolonged fasting. This effect is mainly mediated via catecholamines, which signal through elevation of Cai2+as well as cAMP. We have studied the effect of cAMP on HL expression in cell culture. Overnight incubation of HepG2 cells with 10-300 μM 8-bromo-cyclic AMP resulted in a dose-dependent, up to 50% reduction in secretion of HL, but had no effect on secretion of α1-antitrypsin or overall protein synthesis. HL mRNA levels were decreased 1.5 fold, as determined by semi-quantitative and real-time RT-PCR. In HepG2 cells transiently transfected with human HL (-685/+13) or rat HL (-446/+9) promoter-reporter constructs, cAMP induced a similar dose-dependent suppression of HL promoter activity. cAMP responsiveness in HepG2 cells was mediated by a conserved 10-bp response element at -45/-36, that represents a potential binding site for CCAAT/enhancer-binding protein beta (C/EBPβ). cAMP reduced expression of the 45 kDa C/EBPβ protein and binding of C/EBPβ to the proximal promoter region of the human HL gene by 50%, as determined by immunoblotting and chromatin immunoprecipitation assay, respectively. In human H295R adrenocortical cells, cAMP failed to suppress HL promoter activity, and only slightly reduced C/EBPβ expression. We conclude that the fall in HL expression during prolonged fasting may be mediated through elevation of cAMP and lowering of C/EBPβ expression.

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Keywords Adrenocortical cells, C/EBPβ, Cyclic AMP, Hepatic lipase, Liver cells, Promoter activity, Transcriptional regulation
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van Deursen, D, Botma, G.J, Jansen, H, & Verhoeven, A.J.M. (2008). Down-regulation of hepatic lipase expression by elevation of cAMP in human hepatoma but not adrenocortical cells. Molecular and Cellular Endocrinology, 294(1-2), 37–44. doi:10.1016/j.mce.2008.07.004