Amine oxidase substrates mimic several of the insulin effects on adipocytedifferentiation in 3T3 F442A cells

We have previously reported that substrates of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) exert short-term insulin-like effects in rat adipocytes, such as stimulation of glucose transport. In the present work, we studied whether these substrates could also mimic long-te rm actions of insulin. Adipose differentiation of 3T3 F442A cells, which is highly insulin-dependent, served as a model to test the effects of sustain ed administration of amine oxidase substrates, Daily treatment of confluent cells with 0.75 mM tyramine (a substrate of MAO and SSAO) or benzylamine ( a substrate of SSAO) over 1 week caused the acquisition of typical adipocyt e morphology. The stimulation of protein synthesis and triacylglycerol accu mulation caused by tyramine or benzylamine reached one half of that promote d by insulin. This effect was insensitive to pargyline (an MAO inhibitor). but was inhibited by semicarbazide (an SSAO inhibitor) and by N-acetylcyste ine (an antioxidant agent), suggesting the involvement of the H2O2 generate d during SSAO-dependent amine oxidation, Chronic administration of amine ox idase substrates also induced the emergence of adipose conversion markers, such as aP2, glycerol-3-phosphate dehydrogenase, the glucose transporter GL UT 1. and SSAO itself Moreover, cells treated with amines acquired the same insulin sensitivity regarding glucose transport as adipocytes classically differentiated with insulin. In all, most of the adipogenic effects of amin es were additive to insulin. Our data reveal that amine oxidase substrates partially mimic the adipogenic effect of insulin in cultured preadipocytes. Furthermore, they suggest that SSAO not only represents a novel late marke r of adipogenesis, but could also be directly involved in the triggering of terminal adipocyte differentiation.