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Adipocytes as a source of increased circulating levels of nicotinamide phosphoribosyltransferase/visfatin in active acromegaly.
- Source :
-
The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2012 Apr; Vol. 97 (4), pp. 1355-62. Date of Electronic Publication: 2012 Feb 08. - Publication Year :
- 2012
-
Abstract
- Background: Nicotinamide phosphoribosyltransferase (NAMPT)/visfatin is a widely expressed protein with various effects on glucose and lipid metabolism, cell survival, and inflammation.<br />Aim: We hypothesized that NAMPT was related to metabolic disturbances in active acromegaly.<br />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.<br />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.<br />Conclusions: NAMPT is increased in active acromegaly and may be an inflammatory mediator that causes monocyte infiltration in adipose tissue.
- Subjects :
- Abdominal Fat enzymology
Abdominal Fat immunology
Abdominal Fat metabolism
Abdominal Fat pathology
Acromegaly enzymology
Acromegaly immunology
Adipocytes, White immunology
Adipocytes, White metabolism
Adipocytes, White pathology
Adipogenesis
Adult
Cell Line
Cells, Cultured
Chemokine CCL2 metabolism
Cohort Studies
Cross-Sectional Studies
Cytokines genetics
Cytokines metabolism
Female
Gene Expression Regulation, Enzymologic
Human Growth Hormone blood
Human Growth Hormone metabolism
Humans
Insulin Resistance
Insulin-Like Growth Factor I analysis
Insulin-Like Growth Factor I metabolism
Male
Middle Aged
Nicotinamide Phosphoribosyltransferase genetics
Nicotinamide Phosphoribosyltransferase metabolism
RNA, Messenger metabolism
Subcutaneous Fat enzymology
Subcutaneous Fat immunology
Subcutaneous Fat metabolism
Subcutaneous Fat pathology
Acromegaly blood
Acromegaly pathology
Adipocytes, White enzymology
Adiposity
Cytokines blood
Nicotinamide Phosphoribosyltransferase blood
Subjects
Details
- Language :
- English
- ISSN :
- 1945-7197
- Volume :
- 97
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- The Journal of clinical endocrinology and metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 22319029
- Full Text :
- https://doi.org/10.1210/jc.2011-2417