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©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells
Christian Carpéné, Silvia Garcia-Vicente, Marta Serrano, Luc Marti, Chloé Belles, Miriam Royo, Jean Galitzky, Antonio Zorzano, Xavier Testar
Christian Carpéné, Chloé Belles, Jean Galitzky, Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, INSERM U1048, Institut. National de la Santé et de la Recherche Médicale & Université Paul Sabatier, CHU Rangueil, 31432 Toulouse, France
Silvia Garcia-Vicente, Marta Serrano, Luc Marti, Genmedica Therapeutics S.L., Esplugues de Llobregat, 08950 Barcelona, Spain
Miriam Royo, Combinatorial Chemistry Unit, Barcelona Science Park, University of Barcelona, 08007 Barcelona, Spain
Miriam Royo, CIBER-BBN, Networking Centre on Bioengineering, Biomaterials and Nanomedicine, Barcelona Science Park, 08028 Barcelona, Spain
Antonio Zorzano, Xavier Testar, Departament de Bioquimica i Biomedicina Molecular, Facultat de Biologia, Universitat de Barcelona, 08034 Barcelona, Spain
Antonio Zorzano, Xavier Testar, CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, 08028 Barcelona, Spain
Antonio Zorzano, Institute for Research in Biomedicine (IRB Barcelona), the Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
Author contributions: Carpéné C, Marti L, Zorzano A and Testar X substantially contributed to the conception and design of the study and wrote the paper; Carpéné C, Garcia-Vicente S, Serrano M and Belles C worked in data acquisition; Royo M and Galitzky J performed data analysis and interpretation; all authors drafted the manuscript and approved the final version of the article to be published.
Supported by Institut National de la Santé et de la Recherche Médicale to the INSERM U1048.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse, France. All subjects provided written informed consent to participate in the study, which was approved by the local Ethics Committe: “Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale”.
Institutional animal care and use committee statement: In the performed research in relation with the manuscript #30269 submitted to Word Journal of Diabetes, all the procedures involving animals were reviewed and approved according to INSERM guidelines by the Service de zootechnie of: INSERM/UPS US 006 CREFRE, Toulouse, France, with agreement number C31 555 07, delivered on June 22, 2012.
Conflict-of-interest statement: The authors Garcia-Vicente S, Serrano M and Marti L are or were employees of Genmedica Therapeutics S.L; during the conduct of the study, and declare with all others authors that they do not have any potential conflict of interest in relation to this article.
Data sharing statement: No additional data are available. No data are shared with another study as this manuscript and related data were not published elsewhere. However, collected data under the form of Excel tables saved as .xls or .xlsx and not curated by any antivirus software will be available on request.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Christian Carpéné, Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, INSERM U1048, Institut. National de la Santé et de la Recherche Médicale & Université Paul Sabatier, CHU Rangueil, Cedex 4, 31432 Toulouse, France. christian.carpene@inserm.fr
Telephone: +33-5-61325640
Received: September 22, 2016
Peer-review started: September 23, 2016
First decision: October 20, 2016
Revised: January 6, 2017
Accepted: January 16, 2017
Article in press: January 18, 20117
Published online: April 15, 2017
AIM
To assess in rodent and human adipocytes the antilipolytic capacity of hexaquis(benzylammonium) decavanadate (B6V10), previously shown to exert antidiabetic effects in rodent models, such as lowering free fatty acids (FFA) and glucose circulating levels.
METHODS
Adipose tissue (AT) samples were obtained after informed consent from overweight women undergoing plastic surgery. Comparison of the effects of B6V10 and reference antilipolytic agents (insulin, benzylamine, vanadate) on the lipolytic activity was performed on adipocytes freshly isolated from rat, mouse and human AT. Glycerol release was measured using colorimetric assay as an index of lipolytic activity. The influence of B6V10 and reference agents on glucose transport into human fat cells was determined using the radiolabelled 2-deoxyglucose uptake assay.
RESULTS
In all the species studied, B6V10 exhibited a dose-dependent inhibition of adipocyte lipolysis when triglyceride breakdown was moderately enhanced by β-adrenergic receptor stimulation. B6V10 exerted on human adipocyte a maximal lipolysis inhibition of glycerol release that was stronger than that elicited by insulin. However, B6V10 did not inhibit basal and maximally stimulated lipolysis. When incubated at dose ≥ 10 μmol/L, B6V10 stimulated by twofold the glucose uptake in human fat cells, but - similarly to benzylamine - without reaching the maximal effect of insulin, while it reproduced one-half of the insulin-stimulation of lipogenesis in mouse fat cells.
CONCLUSION
B6V10 exerts insulin-like actions in adipocytes, including lipolysis inhibition and glucose transport activation. B6V10 may be useful in limiting lipotoxicity related to obesity and insulin resistance.
Core tip: This study investigates in murine and human adipocytes the antilipolytic properties of a conjugate of benzylamine and decavanadate (B6V10), already reported to lower hyperglycaemia in diabetic rodents. Data indicated that the conjugate dose-dependently inhibited submaximal activation of lipolysis in all the species studied. Such antilipolytic action deals with the in vivo FFA-lowering properties already described for B6V10 in diabetic rats. B6V10 also activated lipogenesis and glucose transport in fat cells. B6V10 should therefore be useful in preventing the lipotoxicity constituted by the unrestrained lipolytic activity of insulin-resistant adipocytes in obese individuals presenting type 2 diabetes, a state named diabesity.
