Adipocytes as a source of increased circulating levels of nicotinamide phosphoribosyltransferase/visfatin in active acromegaly

J Clin Endocrinol Metab. 2012 Apr;97(4):1355-62. doi: 10.1210/jc.2011-2417. Epub 2012 Feb 8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdominal Fat / enzymology
  • Abdominal Fat / immunology
  • Abdominal Fat / metabolism
  • Abdominal Fat / pathology
  • Acromegaly / blood*
  • Acromegaly / enzymology
  • Acromegaly / immunology
  • Acromegaly / pathology*
  • Adipocytes, White / enzymology*
  • Adipocytes, White / immunology
  • Adipocytes, White / metabolism
  • Adipocytes, White / pathology
  • Adipogenesis
  • Adiposity*
  • Adult
  • Cell Line
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • Cohort Studies
  • Cross-Sectional Studies
  • Cytokines / blood*
  • 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 / blood*
  • Nicotinamide Phosphoribosyltransferase / genetics
  • Nicotinamide Phosphoribosyltransferase / metabolism
  • RNA, Messenger / metabolism
  • Subcutaneous Fat / enzymology
  • Subcutaneous Fat / immunology
  • Subcutaneous Fat / metabolism
  • Subcutaneous Fat / pathology

Substances

  • CCL2 protein, human
  • Chemokine CCL2
  • Cytokines
  • RNA, Messenger
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Nicotinamide Phosphoribosyltransferase
  • nicotinamide phosphoribosyltransferase, human