Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes

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 itsin 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.

Apelin stimulates glucose uptake but not lipolysis in human adipose tissue ex vivo

“…C ATTANÉ and others 25 apelin had a modest effect on glucose uptake in human AT explants and isolated adipocytes. Insulin, at physiological concentrations, stimulated glucose transport in human AT explants twofold above basal, which is in agreement with previous studies performed on human isolated adipocytes (Iglesias-Osma et al 2005, Wanecq et al 2009) or differentiated cultured adipocytes (Hauner et al 1998). It should be noticed that conversion of glucose into fatty acids (de novo lipogenesis) especially in AT is much lower in humans compared to rodents (Zelewski & Swierczyń ski 1990).…”

Visfatin, a novel adipokine, stimulates glucose uptake through the Ca2+-dependent AMPK–p38 MAPK pathway in C2C12 skeletal muscle cells

“…Specifically, it is not clear whether visfatin has insulin-mimetic activity or whether visfatin is a modulator of insulin action. An insulin-like effect has been reported in osteoblasts (Xie et al 2007), and in vitro exposure to visfatin has been shown to increase skeletal muscle GLUT (Harasim et al 2011), but these effects have not been demonstrated in human adipocytes (Wanecq et al 2009). Given the known interaction of visfatin with the insulin receptor, these observations could be attributed to the variety of insulin and visfatin receptors.…”

Circulating and local visfatin/Nampt/PBEF levels in spontaneously hypertensive rats, stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats

“…biosynthesis [2,3]. Recently, visfatin was reported to be a new adipokine which produced and secreted mainly by visceral adipose tissue, and binding to and activating the insulin receptor, inducing an insulinmimic effect both in vitro and in vivo [4], although this effect is still putative [5,6]. Numerous studies have been published to address the possible associations between plasma visfatin levels and various metabolic disorders such as obesity, type 2 diabetes, and metabolic syndrome [7][8][9].…”