Abstract
Visfatin, a protein identified as a secretion product of visceral fat in humans and mice, is also expressed in different anatomical locations, and is known as pre-B cell-colony enhancing factor (PEBF1). It is also an enzyme displaying nicotinamide phosphoribosyltransferase activity (Nampt). The evidence that levels of visfatin correlate with visceral fat mass has been largely debated and widely extended to other regulations in numerous clinical studies and in diverse animal models. On the opposite, the initial findings regarding the capacity of visfatin/Nampt/PEBF1 to bind and to activate the insulin receptor have been scarcely reproduced, and even were contradicted in recent reports. Since the putative insulin mimicking effects of visfatin/Nampt/PEBF1 have never been tested on mature human adipocytes, at least to our knowledge, we tested different human visfatin batches on human fat cells freshly isolated from subcutaneous abdominal fat and exhibiting high insulin responsiveness. Up to 10 nM, visfatin was devoid of clear activatory action on glucose transport in human fat cells while, in the same conditions, insulin increased by more than threefold the basal 2-deoxyglucose uptake. Moreover, visfatin was unable to mimic the lipolysis inhibition induced by insulin. Visfatin definitively cannot be considered as a direct activator of insulin signalling in human fat cells. Nevertheless its in vivo effects on insulin release and on glucose handling deserve to further study the role of this multifunctional extracellular enzyme in obese and diabetic states.
Similar content being viewed by others
References
Atgié, C., Hadj-Sassi, A., Bukowiecki, L., Mauriège, P. (2009): High lipolytic activity and dyslipidemia in a spontaneous hypertensive/NIH corpulent (SHR/N-cp) rat: a genetic model of obesity and type 2 diabetes mellitus. J Physiol Biochem, 65, 33–41.
Bour, S., Iglesias-Osma, M.C., Marti, L., Duro, P. et al. (2006): The imidazoline I2-site ligands BU 224 and 2-BFI inhibit MAO-A and MAO-B activities, hydrogen peroxide production, and lipolysis in rodent and human adipocytes. Eur J Pharmacol, 552, 20–30.
Bour, S., Visentin, V., Gres, S., Saulnier-Blache, J. S., Wabitsch, M., Carpéné, C. (2005): Tyramine, benzylamine, and to a lesser extent histamine, partially mimic the adipogenic effect of insulin in a human preadipocyte cell strain. Inflamm Res, 54, S60-S61.
Carpéné, C., Daviaud, D., Boucher, J., Bour, S. et al. (2006): Short- and long-term insulin-like effects of monoamine oxidase and semicarbazide-sensitive amine oxidase substrates in cultured adipocytesMetabolism, 55, 1397–1405.
Duffaut, C., Bour, S., Prévot, D., Marti, L. et al. (2006): Prolonged treatment with the β3-adrenergic agonist CL 316243 induces adipose tissue remodeling in rat but not in guinea pig: 2) modulation of glucose uptake and monoamine oxidase activity. J Physiol Biochem, 62, 101–112.
Fontana, E., Prevot, D., Visentin, V., Morin, N., Carpéné, C. (2002): Endothelin-1 stimulates glucose transport in murine 3T3 adipocyte lineage, but not in human subcutaneous fat cells. Horm Metab Res, 34, 165–167.
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K. et al. (2005): Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science, 307, 426–430.
Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K. et al. (2007): Retraction. Science, 318, 565.
Garaulet, M., Pérez-Llamas, F., Zamora, S., Tebar, F.J. (2002): Interrelationship between serum lipid profile, serum hormones and other components of the metabolic syndrome. J Physiol Biochem, 58, 151–160.
Hube, F., Hauner, H. (2000): The two tumor necrosis factor receptors mediate opposite effects on differentiation and glucose metabolism in human adipocytes in primary culture. Endocrinology, 141, 2582–2588.
Iglesias-Osma, M.C., Bour, S., García-Barrado, M. J., Visentin, V. et al. (2005): Methylamine but not mafenide mimics insulin-like actvity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism. Pharmacol Res, 52, 475–484.
Jia, S.H., Li, Y., Parodo, J., Kapus, A. et al. (2004): Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest, 113, 1318–1327.
Kim, M.K., Lee, J.H., Kim, H., Park, S.J. et al. (2006): Crystal structure of visfatin/pre-B cell colony-enhancing factor 1/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866. J Mol Biol, 362, 66–77.
Le Flem, G., Pecher, J., Le Flem-Bonhomme, V., Rochette, J. et al. (2009): Human insulin A-chain peptide analog(s) within vitro biological activity. Cell Biochem Funct, 27, 370–377.
Li, L., Yang, G., Shi, S., Yang, M., Liu, H., Boden, G. (2009): The adipose triglyceride lipase, adiponectin and visfatin are downregulated by tumor necrosis factor-alphain vivo. Cytokine, 45, 12–19.
Lorente-Cebrián, S., Bustos, M., Marti, A., Martínez, J.A., Moreno-Aliaga, M.J. (2009): Eicosapentaenoic acid stimulates AMP-activated protein kinase and increases visfatin secretion in cultured murine adipocytes. Clin Sci (Lond), 117, 243–249.
Marrades, M.P., Martínez, J.A., Moreno-Aliaga, M. J. (2008): ZAG, a lipid mobilizing adipokine, is downregulated in human obesity. J Physiol Biochem, 64, 61–66.
Mercader, J., Granados, N., Caimari, A., Oliver, P., Bonet, M. L., Palou, A. (2008): Retinol-binding protein 4 and nicotinamide phosphoribosyltransferase/visfatin in rat obesity models. Horm Metab Res, 40, 467–472.
Minet-Ringuet, J., Even, P.C., Valet, P., Carpéné, C. et al. (2007): Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment. Mol Psychiatry, 12, 562–571.
Moschen, A., Kaser, A., Enrich, B., Mosheimer, B. et al. (2007): Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol, 178, 1748–1758.
Ognjanovic, S., Bao, S., Yamamoto, S.Y., Garibay-Tupas, J., Samal, B., Bryant-Greenwood, G.D. (2001): Genomic organization of the gene coding for human pre-B-cell colony enhancing factor and expression in human fetal membranes. J Mol Endocrinol, 26, 107–117.
Ognjanovic, S., Tashima, L.S., Bryant-Greenwood, G.D. (2003): The effects of pre-B-cell colony-enhancing factor on the human fetal membranes by microarray analysis. Am J Obstet Gynecol, 189, 1187–1195.
Pérez-Echarri, N., Pérez-Matute, P., Marcos-Gómez, B., Martínez, J. A., Moreno-Aliaga, M.J. (2009): Effects of eicosapentaenoic acid ethyl ester on visfatin and apelin in lean and overweight (cafeteria diet-fed) rats. Br J Nutr, 101, 1059–1067.
Revollo, J.R., Körner, A., Mills, K.F., Satoh, A. et al. (2007): Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab, 6, 363–375.
Samal, B., Sun, Y., Stearns, G., Xie, C., Suggs, S., McNiece, I. (1994): Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol, 14, 1431–1437.
Samara, A., Pfister, M., Marie, B., Visvikis-Siest, S. (2008): Visfatin, low-grade inflammation and body mass index (BMI). Clin Endocrinol (Oxf), 69, 568–574.
Sancho, V., Nuche, B., Arnés, L., Cancelas, J. et al. (2007): The action of GLP-1 and exendins upon glucose transport in normal human adipocytes, and on kinase activity as compared to morbidly obese patients. Int J Mol Med, 19, 961–966.
Sommer, G., Garten, A., Petzold, S., Beck-Sickinger, A. G. et al. (2008): Visfatin/PBEF/Nampt: structure, regulation and potential function of a novel adipokine. Clin Sci (Lond), 115, 13–23.
Tanaka, M., Nozaki, M., Fukuhara, A., Segawa, K. et al. (2007): Visfatin is released from 3T3-L1 adipocytes via a non-classical pathway. Biochem Biophys Res Commun, 359, 194–201.
Xie, H., Tang, S.Y., Luo, X. H., Huang, J. et al. (2007): Insulin-like effects of visfatin on human osteoblasts. Calcif Tissue Int, 80, 201–210.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wanecq, E., Prévot, D. & Carpéné, C. Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes. J Physiol Biochem 65, 351–359 (2009). https://doi.org/10.1007/BF03185930
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF03185930