Semicarbazide-sensitive amine oxidase substrates stimulate glucose transport and inhibit lipolysis in human adipocytes

Semicarbazide-sensitive amine oxidases (SSAO) are widely distributed enzyme s scavenging biogenic or exogenous amines and generating hydrogen peroxide. We asked whether human adipose tissue could express SSAO. Since hydrogen p eroxide exhibits pharmacological insulin-like effects, we also tested wheth er its endogenous production by SSAO could mimic several insulin effects on adipocytes, such as stimulation of glucose uptake and inhibition of lipoly sis. The benzylamine oxidation by human adipose tissue was inhibited by sem icarbazide or hydralazine and resistant to pargyline or selegiline. It was due to an SSAO activity localized in adipocyte membranes. A protein of 100- kDa and a 4-kb mRNA corresponding to SSAO were identified in either mammary or abdominal subcutaneous fat depots. In isolated adipocytes, SSAO oxidize d similarly benzylamine and methylamine that dose dependently stimulated gl ucose transport in a semicarbazide-sensitive manner. Antioxidants also inhi bited the benzylamine and methylamine effects. Moreover, the ability of div erse substrates to be oxidized by adipocytes was correlated to their effect on glucose transport. Benzylamine and methylamine exerted antilipolytic ef fects with a maximum attained at 1 mM. These results show that human adipoc ytes express a membrane-bound SSAO that not only readily oxidizes exogenous amines and generates H2O2, but that also interplays with glucose and lipid metabolism by exerting insulin-like actions. Based on these results and th e fact that variations in plasma levels of the soluble form of SSAO have be en previously reported in diabetes, we propose that determination of adipoc yte SSAO, feasible on subcutaneous microbiopsies, could bring relevant info rmation in pathologies such as obesity or diabetes.