Leptin-mediated reactive oxygen species production does not significantly affect primary mouse hepatocyte functions in vitro.

Ben Schroyen, Eduardo MacHado Guimaraes, Laurent Dolle, Christophe Empsen, Marc Nyssen, Albert Geerts, Isabelle Colle, Leonardus Van Grunsven

Research output: Contribution to journalArticle

16 Citations (Scopus)


AIM: Direct and indirect effects of leptin on hepatic stellate cells (HSCs) have been documented in the literature, whereas little is known about leptin's actions on hepatocytes. Leptin mediates its profibrogenic and proinflammatory effects on HSCs in part through the production of intracellular reactive oxygen species (ROS). In this study, we focus our analysis on leptin-induced ROS production in hepatocytes.

METHODS: The expression of leptin receptor isoforms on primary mouse liver cells was examined by real-time quantitative-PCR and western blotting. Cultures were exposed to leptin in combination with inhibitors for reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, MAP kinase/ERK kinase 1 (MEK1) or janus kinase 2 (JAK2). ROS levels were quantified by measuring fluorescence. The effects of leptin on hepatocyte functions and programmed cell death were evaluated by fluorescent or luminescent assays.

RESULTS: Leptin induced ROS production in primary hepatocytes by 150-450%, compared with a 20-30% increase in HSCs and liver sinusoidal endothelial cells (LSECs). This ROS production could be inhibited by NADPH oxidase, MEK1 and JAK2 inhibitors. Western blotting indicated that mouse HSCs and LSECs mainly express short leptin receptor isoforms, whereas hepatocytes appeared to express both short and long isoform(s). Leptin-induced ROS production in db/db hepatocytes did not differ from wild-type mice. Finally, leptin had no negative influence on primary hepatocyte functions.

CONCLUSION: Leptin induced higher ROS levels in primary hepatocytes than in LSECs and HSCs, depending on NADPH oxidase, MEK1 and JAK2 signalling but not on the long leptin receptor isoform. Furthermore, leptin exposure did not influence primary hepatocyte functionality negatively
Original languageEnglish
Pages (from-to)1370-1380
Number of pages11
JournalEuropean Journal of Gastroenterology and Hepatology
Issue number12
Publication statusPublished - Dec 2012

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