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 tissue suggests the expression of the catecholamine-degrading enzyme monoamine oxidases and of catecholamine transport systems in adipocytes. In the present study, we identified and characterized the monoamine oxidases and an extraneuronal noradrenaline transporter expressed in human adipocytes. Enzyme assays using the monoamine oxidase A/B substrate [14C]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 [14C]tyramine oxidation and Western and Northern blot analyses showed that mRNAs and proteins related to both monoamine oxidases A and B were expressed in adipocytes. Quantification of each enzyme isoform performed by enzyme assay and Western blot showed that monoamine oxidase A was predominant, representing 70-80% of the total enzyme activity. In uptake experiments, the monoamine oxidase substrate [3H]noradrenaline was transported into white adipocytes (Vmax 0.81+/-0.3 nmol/30 min/100 mg of lipid, Km 235+/-104 microM). The inhibition of [3H]noradrenaline uptake by specific inhibitors indicated that white human adipocytes contain an extraneuronal-type noradrenaline transporter. Competition studies of [14C]tyramine oxidation showed that noradrenaline is metabolized by monoamine oxidases in intact cells. In conclusion, the concomitant expression of monoamine oxidases and of a noradrenaline transporter in human white adipocytes supports the role of the adipose tissue in the clearance of peripheral catecholamines. These results suggest that adipocytes should be considered as a previously unknown potential target of drugs acting on monoamine oxidases and noradrenaline transporters.
Pizzinat
N
N
Institut National de la Santé et de la Recherche Médicale U388, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Marti
L
L
Remaury
A
A
Leger
F
F
Langin
D
D
Lafontan
M
M
Carpéné
C
C
Parini
A
A
D000273:Adipose Tissue / Q000201:enzymology* / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000378:metabolism; D000328:Adult; D001692:Biological Transport; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis; D008995:Monoamine Oxidase / Q000096:biosynthesis*; D009638:Norepinephrine / Q000378:metabolism*
D000316:Adrenergic alpha-Agonists; D007527:Isoenzymes; D008995:Monoamine Oxidase; D009638:Norepinephrine