1 research outputs found
Effects of Chemical Structures Interacting with Amine Oxidases on Glucose, Lipid and Hydrogen Peroxide Handling by Human Adipocytes
Benzylamine is a natural molecule present in food and edible plants, capable of activating
hexose uptake and inhibiting lipolysis in human fat cells. These effects are dependent on its oxidation
by amine oxidases present in adipocytes, and on the subsequent hydrogen peroxide production,
known to exhibit insulin-like actions. Virtually, other substrates interacting with such hydrogen
peroxide-releasing enzymes potentially can modulate lipid accumulation in adipose tissue. Inhibition
of such enzymes has also been reported to influence lipid deposition. We have therefore studied
in human adipocytes the lipolytic and lipogenic activities of pharmacological entities designed to
interact with amine oxidases highly expressed in this cell type: the semicarbazide-sensitive amine
oxidase (SSAO also known as PrAO or VAP-1) and the monoamine oxidases (MAO). The results
showed that SZV-2016 and SZV-2017 behaved as better substrates than benzylamine, releasing
hydrogen peroxide once oxidized, and reproduced or even exceeded its insulin-like metabolic effects
in fat cells. Additionally, several novel SSAO inhibitors, such as SZV-2007 and SZV-1398, have been
evidenced and shown to inhibit benzylamine metabolic actions. Taken as a whole, our findings
reinforce the list of molecules that influence the regulation of triacylglycerol assembly/breakdown,
at least in vitro in human adipocytes. The novel compounds deserve deeper investigation of their
mechanisms of interaction with SSAO or MAO, and constitute potential candidates for therapeutic
use in obesity and diabetes