High expression of monoamine oxidases in human white adipose tissue: Evidence for their involvement in noradrenaline clearance

The clearance of plasma adrenaline and noradrenaline by human adipose tissu e suggests the expression of the catecholamine-degrading enzyme monoamine o xidases and of catecholamine transport systems in adipocytes. In the presen t study, we identified and characterized the monoamine oxidases and an extr aneuronal noradrenaline transporter expressed in human adipocytes. Enzyme a ssays using the monoamine oxidase A/B substrate [C-14]tyramine showed that abdominal and mammary human adipocytes contain one of the highest monoamine oxidase activities in the body. Characterization of the enzyme isoforms by inhibition profiles of [C-14]tyramine oxidation and Western and Northern b lot analyses showed that mRNAs and proteins related to both monoamine oxida ses A and B were expressed in adipocytes. Quantification of each enzyme iso form performed by enzyme assay and Western blot showed that monoamine oxida se A was predominant, representing 70-80% of the total enzyme activity. In uptake experiments, the monoamine oxidase substrate [H-3]noradrenaline was transported into white adipocytes (V-max 0.81 +/- 0.3 nmol/30 min/100 mg of lipid, K-m 235 +/- 104 mu M). The inhibition of [3H]noradrenaline uptake b y specific inhibitors indicated that white human adipocytes contain an extr aneuronal-type noradrenaline transporter. Competition studies of [C-14]tyra mine oxidation showed that noradrenaline is metabolized by monoamine oxidas es in intact cells. In conclusion, the concomitant expression of monoamine oxidases and of a noradrenaline transporter in human white adipocytes suppo rts the role of the adipose tissue in the clearance of peripheral catechola mines. These results suggest that adipocytes should be considered as a prev iously unknown potential target of drugs acting on monoamine oxidases and n oradrenaline transporters. BIOCHEM PHARMACOL 58;11:1735-1742, 1999. (C) 199 9 Elsevier Science Inc.