Expression of adrenomedullin in adipose tissue of lean and obese women.
OBJECTIVE
Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity.


METHODS
Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions.


METHODS
AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR.


RESULTS
A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor alpha mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome.


CONCLUSIONS
Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.
Paulmyer-Lacroix
O
O
Inserm UMR 626, UFR de Médecine secteur Timone, 27 Bd Jean Moulin, 13385 Marseille cedex 5, France. odile.lacroix-paulmyer@mail.ap-hm.fr
Desbriere
R
R
Poggi
M
M
Achard
V
V
Alessi
M-C
MC
Boudouresque
F
F
Ouafik
L'H
L
Vuaroqueaux
V
V
Labuhn
M
M
Dutourand
A
A
Grino
M
M
D000273:Adipose Tissue / Q000378:metabolism*; D053607:Adrenomedullin; D000328:Adult; D000886:Anthropometry; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D010455:Peptides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D053607:Adrenomedullin