The enzymatic machinery for ADMA synthesis and degradation is fully expressed in human adipocytes.
BACKGROUND
The endogenous inhibitor of nitric oxide synthase (NOS), asymmetric dimethylarginine (ADMA), is implicated in endothelial dysfunction and is a marker of renal disease progression and cardiovascular (CV) complications. Various cell species exhibit the enzymatic system that generates and degrades this methylarginine, but it is unknown whether this machinery is expressed in adipocytes. The question is relevant because adipocyte-derived mediators are implicated both in renal and cardiovascular diseases.


METHODS
We measured ADMA concentration in pure adipocytes in culture and measured mRNA levels of the enzymes involved in ADMA metabolism (real-time polymerase chain reaction) both in pure adipocytes in culture and in adipose tissue harvested in 9 healthy subjects. These enzymes included protein arginine N-methyltransferases type I (PRMTs) involved in ADMA synthesis, dimethylarginine dimethylaminohydrolases (DDAHs) responsible for ADMA degradation and constitutive and inducible forms of NOS (i.e., NOS1, NOS2A and NOS3 genes), the main functional target of ADMA.


RESULTS
Human adipocytes express the whole gene set that codes for the enzymatic system responsible for the biosynthesis and the degradation of ADMA, and this methylarginine is actually released by adipocytes in culture. NOS gene isoforms have a low level of expression in human adipose tissue, indicating that putative functions of ADMA in fat cells may be in part mediated by mechanisms other than NOS inhibition.


CONCLUSIONS
Human adipocytes produce ADMA and express the full enzymatic machinery responsible for ADMA metabolism. Studying the functional implication of these findings may be of relevance for clarifying the role of fat mass expansion in human disease.
Spoto
Belinda
B
CNR-IBIM, National Research Council Institute of Biomedicine-Clinical Epidemiology and Physiopathology of Renal Disease and Hypertension & Urology Unit, Reggio Calabria - Italy.
Parlongo
Rosa M
RM
Parlongo
Giovanna
G
Sgro'
Edoardo
E
Zoccali
Carmine
C
D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050152:Intra-Abdominal Fat / Q000201:enzymology / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000201:enzymology / Q000378:metabolism*
D007527:Isoenzymes; D012333:RNA, Messenger; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D011484:Protein-Arginine N-Methyltransferases; D000581:Amidohydrolases; C059999:dimethylargininase