Adipocytes as a source of increased circulating levels of nicotinamide phosphoribosyltransferase/visfatin in active acromegaly.
BACKGROUND
Nicotinamide phosphoribosyltransferase (NAMPT)/visfatin is a widely expressed protein with various effects on glucose and lipid metabolism, cell survival, and inflammation.


OBJECTIVE
We hypothesized that NAMPT was related to metabolic disturbances in active acromegaly.


METHODS
Body composition, glucose metabolism, and NAMPT levels were measured in 47 patients with active, untreated acromegaly and 24 age-, sex-, and body mass index-matched controls. The in vitro effects of GH/IGF-I on NAMPT expression in human sc adipocytes (SCA), visceral adipocytes, osteoblasts, and hepatocytes were studied. The effects of overnight incubation with the highly specific NAMPT inhibitor FK866 on the GH-stimulated monocyte chemotactic protein-1 and IL-6 expression in mature SCA were evaluated.


RESULTS
NAMPT was increased in active acromegaly (P = 0.004) and correlated negatively with limb (arms + legs) fat percentage (% fat, r = -0.32; P = 0.032). After adjusting for age, gender, leptin, and GH, the circulating NAMPT correlated negatively with limb and total body fat percentage (% fat limbs, r = -0.43, P = 0.006; % fat total body, r = -0.36, P = 0.022) and correlated positively with limb and total body lean percentage (% lean limbs, r = 0.31, P = 0.047; % lean total body, r = 0.33, P = 0.034). No correlation between NAMPT and glucose metabolic parameters was found. In vitro studies revealed that GH increased NAMPT expression in adipocytes. The inhibition of NAMPT enzymatic activity attenuated GH-induced monocyte chemotactic protein-1 expression in SCA.


CONCLUSIONS
NAMPT is increased in active acromegaly and may be an inflammatory mediator that causes monocyte infiltration in adipose tissue.
Section of Specialized Endocrinology, Oslo University Hospital, Rikshospitalet, Songnsvannsveien 20, N-0027 Oslo, Norway. nicola@ous-hf.no
Nicoleta C
NC
Olarescu
Thor
T
Ueland
Tove
T
Lekva
Tuva B
TB
Dahl
Bente
B
Halvorsen
Pål
P
Aukrust
Jens
J
Bollerslev
D050153:Abdominal Fat / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000172:Acromegaly / Q000097:blood* / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D052438:Adipocytes, White / Q000201:enzymology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis; D050154:Adiposity; D000328:Adult; D002460:Cell Line; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000201:enzymology / Q000276:immunology / Q000378:metabolism / Q000473:pathology
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; D012333:RNA, Messenger; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human