Endocrine Abstracts (2011) 26 P192

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

C Olarescu1, T Ueland1,2, T Lekva1,2, T B Dahl2, P Aukrust2, B Halvorsen2 & J Bollerslev1,3

1Section of Specialized Endocrinology, Rikshospitalet, Oslo University Hospital, Oslo, Norway; 2Research Institute for Internal Medicine, Rikshospitalet, Oslo University Hospital, Oslo, Norway; 3Faculty of Medicine, University of Oslo, Norway, Oslo, Norway.

Background: Nicotinamide phosphoribosyltransferase (NAMPT)/PBEF/visfatin is a widely expressed cytokine with various effects on glucose and lipid metabolism, cell survival, and inflammation. Despite a favorable body composition profile, acromegalic patients present insulin resistance, increased cardiovascular risk, and higher incidence of secondary tumors.

Aim: Based on its relation to glucose and lipid metabolism and inflammation we hypothesized that NAMPT could be related to the metabolic disturbances in patients with acromegaly.

Methods: Body composition, glucose metabolism (glucose, insulin, HOMA-IR, HOMA-B), leptin and NAMPT levels were measured in 47 patients with active acromegaly (26 women, 21 men) and 25 matched control subjects. In vitro effects of GH/IGF1 on NAMPT expression in peripheral blood mononuclear cells (PBMC), hepatocytes, osteoblasts, human subcutaneous (SCA) and visceral (VA) adipocytes were studied.

Results: NAMPT was markedly increased in acromegaly in both sexes (P<0.01). NAMPT levels correlated, before and following adjustment for age, gender and leptin, negatively with total body fat mass (% fat: r=−0.35, P=0.03) and arms fat mass (% fat: r=−0.37, P=0.02) and positively with total lean mass (% lean: r=0.35, P=0.03) and arms lean mass (% lean: r=0.42, P=0.008). No correlation between NAMPT and glucose metabolic parameters was demonstrated. In vitro studies revealed that GH increases NAMPT expression during differentiation of subcutaneous (SCA) and visceral (VA) preadipocytes and in mature SCA, but not in mature VA, PBMC, osteoblasts or hepatocytes.

Conclusions: NAMPT levels are increased in active acromegaly with no relation to glucose metabolism. Our in vitro findings may suggest that GH directly could induce NAMPT expression in SCA, and the positive correlation of NAMPT with lean mass suggests that skeletal muscles could be another source of NAMPT in active acromegaly.

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