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

Abstract

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-term actions of insulin. Adipose differentiation of 3T3 F442A cells, which is highly insulin-dependent, served as a model to test the effects of sustained 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 adipocyte morphology. The stimulation of protein synthesis and triacylglycerol accumulation caused by tyramine or benzylamine reached one half of that promoted by insulin. This effect was insensitive to pargyline (an MAO inhibitor), but was inhibited by semicarbazide (an SSAO inhibitor) and by N-acetylcysteine (an antioxidant agent), suggesting the involvement of the H(2)O(2) generated during SSAO-dependent amine oxidation. Chronic administration of amine oxidase substrates also induced the emergence of adipose conversion markers, such as aP2, glycerol-3-phosphate dehydrogenase, the glucose transporter GLUT4, 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 amines 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 marker of adipogenesis, but could also be directly involved in the triggering of terminal adipocyte differentiation.

Semicarbazide‐sensitive amine oxidase overexpression has dual consequences: insulin mimicry and diabetes‐like complications

“…Here we show that SSAO activity from endothelial cells can also promote skeletal muscle glucose transport. In keeping with these observations it has previously been observed that SSAO substrates, including methylamine, promote in vitro insulin-like effects on adipocyte (2,6,7,32) and smooth muscle cell metabolism (3) through the production of hydrogen peroxide. This reactive oxygen species has been implicated in the insulin intracellular signaling pathway through its capacity to inhibit protein tyrosine phosphatase activity and hence enhance protein phosphorylation in response to insulin (33).…”

Expression of the semicarbazide-sensitive amine oxidase in articular cartilage: its role in terminal differentiation of chondrocytes in rat and human

“…We and others have previously shown that SSAO activation promotes adipocyte maturation 8,35 and stimulates glucose transport through the GLUT transporters via H 2 O 2 in adipocytes 31 and VSMC 9 . Glucose is of major importance for the biosynthesis of matrix glycosaminoglycans, and for the maturation of chondrocytes 36e39 .…”

The nuclear receptor PPARγ individually responds to serotonin- and fatty acid-metabolites

“…In addition to the receptor‐mediated action, 5‐HT also coordinates fat metabolism and feeding through a receptor‐independent mechanism (Srinivasan et al , 2008). Other reports described the association between MAO expression and insulin sensitization (Fontana et al , 2001) and that between MAO polymorphism and obesity (Fuemmeler et al , 2008). These reports suggested that 5‐HT metabolites are not simply degradation products of 5‐HT, but may have additional functions.…”