Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans

Abstract

Aims/hypothesisNicotinamide phosphoribosyltransferase (NAMPT) is a multifunctional protein potentially involved in obesity and glucose metabolism. We systematically studied the association between circulating NAMPT, obesity, interventions and glucose metabolism and investigated potential underlying inflammatory mechanisms.MethodsFasting morning NAMPT serum levels were measured in cohorts of lean vs obese children, cohorts of intervention by lifestyle, exercise and bariatric surgery, and during an OGTT. In addition, mRNA expression, protein production and enzymatic activity of NAMPT were assessed from isolated leucocytes and subpopulations.ResultsCirculating NAMPT was significantly elevated in obese compared with lean children and declined after obesity interventions concomitantly with the decline in BMI, high-sensitivity C-reactive protein (hsCrP) and leucocyte counts. Circulating NAMPT significantly correlated with glucose metabolism and cardiovascular variables in univariate analyses, but only the association with glucose response during an OGTT was independent from BMI. We therefore assessed the NAMPT dynamic following an oral glucose load and found a significant decline of NAMPT levels to 77.0 ± 0.1% as a function of time, and insulin-to-glucose ratio during an OGTT in obese insulin-resistant adolescents. Circulating NAMPT was, however, most strongly associated with leucocyte counts (r = 0.46, p < 0.001). The leucocyte count itself determined significantly and independently from BMI insulin resistance in multiple regression analyses. We systematically evaluated NAMPT expression among several tissues and found that NAMPT was predominantly expressed in leucocytes. In subsequent analyses of leucocyte subpopulations, we identified higher NAMPT protein concentrations in lysates of granulocytes and monocytes compared with lymphocytes, whereas granulocytes secreted highest amounts of NAMPT protein into cell culture supernatant fractions. We confirmed nicotinamide mononucleotide enzymatic activity of NAMPT in all lysates and supernatant fractions. In monocytes, NAMPT release was significantly stimulated by lipopolysaccharide (LPS) exposure.ConclusionsLeucocytes are a major source of enzymatically active NAMPT, which may serve as a biomarker or even mediator linking obesity, inflammation and insulin resistance.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-010-2042-z) contains supplementary material, which is available to authorised users.

Single and Concurrent Effects of Endurance and Resistance Training on Plasma Visfatin, Insulin, Glucose and Insulin Resistance of Non-Athlete Men with Obesity

“…Weight loss after exercise program causes reduced serum levels of visfatin (15) and this reinforces the theory that reduced visfatin is associated with improved insulin sensitivity (3). Much evidence show that physical activity is associated with reduced cardiovascular diseases which cause mortality in the general population, and in patients with type 2 diabetes mellitus.…”

The role of adipocytokines in the pathogenesis of knee joint osteoarthritis

“…Its role in metabolic processes is still controversial, but it has been reported that the properties of visfatin are similar to insulin. It has been suggested that the levels of visfatin are higher in obese [44,45] and in OA patients [46]. In an experimental study, it has been found that visfatin level could be down-regulated by the overexpression of miR34a, which binds directly to the 3′UTR of visfatin mRNA.…”

Neuronal NAMPT is Released after Cerebral Ischemia and Protects against White Matter Injury

“…Instead, it can be secreted into the extracellular space or into the blood via a non-classical secretory mechanism 13 by a number of cell types, such as adipocytes, hepatocytes, macrophages, and leukocytes. [14][15][16] Whether neuronal cells also secrete eNAMPT and its potential function in the CNS remain unknown. In the present study, we observed that transgenic mice overexpressing NAMPT in a neuron-specific manner were highly resistant to focal cerebral ischemic brain damage.…”