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Die Nicotinamid-N-Methyltransferase (NNMT) ist ein vor kurzem neu erkannter Regulator der Energiehomöostase im Fettgewebe. Die Hemmung von NNMT durch 1-Methylnicotinamid (1-MN) führt dosisabhängig zu einer Steigerung der Glycerolfreisetzung aus 3T3-L1-Adipozyten im Sinne einer gesteigerten Lipolyse. Die Sekretion von Adiponektin und Leptin wird durch 1-Methylnicotinamid nicht messbar verändert. Um die Messwerte unterschiedlich stark ausdifferenzierter Zellkulturpassagen miteinander vergleichen zu können, wurde eine photometrische Methode entwickelt und publiziert. Die Ergebnisse dieser Dissertation zeigen, dass NNMT die Lipolyse in Fettzellen reguliert, was zum besseren Verständnis der physiologischen Funktion dieser im Fettgewebe neu entdeckten Methyltransferase beiträgt.
Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium
(2016)
A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response.