Adipocytes as a Source of Increased Circulating Levels of Nicotinamide Phosphoribosyltransferase/Visfatin in Active Acromegaly

作者:Olarescu Nicoleta C*; Ueland Thor; Lekva Tove; Dahl Tuva B; Halvorsen Bente; Aukrust Pal; Bollerslev Jens
来源:Journal of Clinical Endocrinology & Metabolism, 2012, 97(4): 1355-1362.
DOI:10.1210/jc.2011-2417

摘要

Background: Nicotinamide phosphoribosyltransferase (NAMPT)/visfatin is a widely expressed protein with various effects on glucose and lipid metabolism, cell survival, and inflammation.
Aim: 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. (J Clin Endocrinol Metab 97: 1355-1362, 2012)

  • 出版日期2012-4