Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Jan 27, 2022; 13(1): 15-34
Published online Jan 27, 2022. doi: 10.4331/wjbc.v13.i1.15
Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats
Christian Carpéné, Luc Marti, Nathalie Morin
Christian Carpéné, Luc Marti, Nathalie Morin, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, Toulouse 31342, France
Nathalie Morin, Faculté de Pharmacie de Paris, Paris University, Paris 75270, France
Author contributions: Carpéné C designed the studies, performed hexose uptake assays and literature review, and wrote the manuscript; Marti L performed binding studies, rat experiments, and data analysis, and contributed to the literature review; Morin N performed immunoblots and data analysis, and revised the manuscript.
Supported by Recurrent Grants from 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.
Institutional animal care and use committee statement: Rats were housed and manipulated according to the INSERM guidelines and European Directive 2010/63/UE by competent and expert technicians or researchers in animal care facilities with agreements number A 31 555 04 to C 31 555 011. The experimental protocol was approved by the local ethical committee CEEA nb122.
Conflict-of-interest statement: All authors declare no competing financial interests for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Christian Carpéné, PhD, Senior Researcher, Institut des Maladies Métaboliques et Cardiovasculaires, INSERM, CHU Rangueil, Bat. L4, BP 84225, Toulouse 31342, France. christian.carpene@inserm.fr
Received: March 26, 2021
Peer-review started: March 26, 2021
First decision: July 8, 2021
Revised: July 9, 2021
Accepted: January 13, 2022
Article in press: January 13, 2022
Published online: January 27, 2022
Processing time: 301 Days and 14.5 Hours
Abstract
BACKGROUND

Despite overt insulin resistance, adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids.

AIM

To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide, since it is produced by monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) in adipocytes.

METHODS

3H-2-deoxyglucose uptake (2-DG) was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine. 14C-tyramine oxidation and binding of imidazolinic radioligands [3H-Idazoxan, 3H-(2-benzofuranyl)-2-imidazoline] were studied in adipocytes, the liver, and muscle. The influence of in vivo administration of tyramine + vanadium on glucose handling was assessed in lean and obese rats.

RESULTS

2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats, when compared to their lean littermates. Tyramine and benzylamine activation of hexose uptake was vanadate-dependent and was also limited, while MAO was increased and SSAO decreased. These changes were adipocyte-specific and accompanied by a greater number of imidazoline I2 binding sites in the obese rat, when compared to the lean. In vitro, tyramine precluded the binding to I2 sites, while in vivo, its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese rats.

CONCLUSION

The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site number. However, probably as a consequence of SSAO down-regulation, the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant adipocytes. The adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.

Keywords: Obesity; Adipocyte; Amine oxidases; Imidazoline binding sites; Creatine kinase B; Idazoxan; Lipogenesis; Hydrogen peroxide; Glucose uptake

Core Tip: The substrates of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) partly reproduce the stimulatory effect of insulin on sugar entry in rat fat cells. Especially when combined with vanadium, tyramine and benzylamine mimic more than 70% of the insulin stimulation of glucose uptake. Unfortunately, such insulin activation of glucose utilization is strongly diminished in the genetically obese Zucker rat, an animal model of the metabolic syndrome. In this insulin-resistant and obese rat, the stimulation of glucose transport by tyramine is decreased as much as that of insulin, while the effect of benzylamine is even more altered. SSAO, responsible for benzylamine oxidation, is down-regulated in adipocytes from obese Zucker rats. In contrast, MAO, which predominantly supports the oxidation of tyramine, is increased, apparently not in a sufficient manner to reach the same hexose uptake activation seen in fat cells from lean rats. However, this greater ability to oxidize tyramine was found only in white adipocytes from obese rats since no change was found in the liver or skeletal muscle when compared to lean controls. Moreover, increased MAO activity in the large adipocytes of obese rats was accompanied by an enlarged number of imidazoline binding sites, previously described to be located on MAO. Since the repeated subcutaneous administration of tyramine plus vanadate is somewhat capable of reducing plasma glucose and triglycerides in obese rats, SSAO, MAO, and its associated imidazoline I2 sites deserve further studies with respect to their mimicking insulin action on glucose and lipid metabolism in fat cells.