Selegiline reduces adiposity induced by high‐fat, high‐sucrose diet in male rats

Nagy, Csilla Terézia; Koncsos, Gábor; Varga, Zoltán V.; Baranyai, Tamás; Tuza, Sebestyén; Kassai, Ferenc; Ernyey, Alíz Judit; Gyertyán, István; Király, Kornél; Oláh, Attila; Radovits, Tamás; Merkely, Béla; Bukosza, Nóra; Szénási, Gábor; Hamar, Péter; Máthé, Domokos; Szigeti, Krisztián; Pelyhe, Csilla; Jelemenský, Marek; Onódi, Zsófia; Helyes, Zsuzsanna; Schulz, Rainer; Giricz, Zoltán; Ferdinándy, Péter

doi:10.1111/bph.14437

Cited by 16 publications

(12 citation statements)

References 52 publications

(57 reference statements)

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“…The MAO-B inhibitor selegiline was very recently reported by Nagy and co-workers to reduce adiposity induced by a high-fat, high-sucrose diet in male rats without influencing body weight [25]. Similarly, the MAO inhibitor phenelzine has been shown to reduce body fat content in mice fed a standard rodent chow without a decrease in body weight gain or food intake [22].…”

Section: Past and Present Observations Of Amine Oxidase Inhibitor mentioning

confidence: 99%

Past, Present and Future Anti-Obesity Effects of Flavin-Containing and/or Copper-Containing Amine Oxidase Inhibitors

et al. 2019

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Background: Two classes of amine oxidases are found in mammals: those with a flavin adenine dinucleotide as a cofactor, such as monoamine oxidases (MAO) and lysine-specific demethylases (LSD), and those with copper as a cofactor, including copper-containing amine oxidases (AOC) and lysyl oxidases (LOX). All are expressed in adipose tissue, including a semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) strongly present on the adipocyte surface. Methods: Previously, irreversible MAO inhibitors have been reported to limit food intake and/or fat extension in rodents; however, their use for the treatment of depressed patients has not revealed a clear anti-obesity action. Semicarbazide and other molecules inhibiting SSAO/VAP-1 also reduce adiposity in obese rodents. Results: Recently, a LOX inhibitor and a subtype-selective MAO inhibitor have been shown to limit fattening in high-fat diet-fed rats. Phenelzine, which inhibits MAO and AOC, limits adipogenesis in cultured preadipocytes and impairs lipogenesis in mature adipocytes. When tested in rats or mice, phenelzine reduces food intake and/or fat accumulation without cardiac adverse effects. Novel amine oxidase inhibitors have been recently characterized in a quest for promising anti-inflammatory or anti-cancer approaches; however, their capacity to mitigate obesity has not been studied so far. Conclusions: The present review of the diverse effects of amine oxidase inhibitors impairing adipocyte differentiation or limiting excessive fat accumulation indicates that further studies are needed to reveal their potential anti-obesity properties.

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Section: Past and Present Observations Of Amine Oxidase Inhibitor mentioning

confidence: 99%

Past, Present and Future Anti-Obesity Effects of Flavin-Containing and/or Copper-Containing Amine Oxidase Inhibitors

et al. 2019

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“…Importantly, a recent study reported that the MAO-B inhibitor, selegiline, reduced subcutaneous and visceral adiposity as well as inflammation of white adipose tissue in a rat model of diet-induced obesity (with high-fat and high-sucrose diet); these effects strongly suggest a beneficial role of MAO inhibitors as an adjuvant therapy in patients with obesity, metabolic syndrome, and type 2 diabetes [74].…”

Section: Mao and Obesity/metabolic Syndromementioning

confidence: 99%

Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden

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et al. 2019

Oxidative Medicine and Cellular Longevity

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Monoamine oxidases (MAO) with 2 isoforms, A and B, located at the outer mitochondrial membrane are flavoenzyme membranes with a major role in the metabolism of monoaminergic neurotransmitters and biogenic amines in the central nervous system and peripheral tissues, respectively. In the process of oxidative deamination, aldehydes, hydrogen peroxide, and ammonia are constantly generated as potential deleterious by-products. While being systematically studied for decades as sources of reactive oxygen species in brain diseases, compelling evidence nowadays supports the role of MAO-related oxidative stress in cardiovascular and metabolic pathologies. Indeed, oxidative stress and chronic inflammation are the most common pathomechanisms of the main noncommunicable diseases of our century. MAO inhibition with the new generation of reversible and selective drugs has recently emerged as a pharmacological strategy aimed at mitigating both processes. The aim of this minireview is to summarize available information regarding the contribution of MAO to the vascular oxidative stress and endothelial dysfunction in hypertension, metabolic disorders, and chronic kidney disease, all conditions associated with increased inflammatory burden.

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“…We extended a similar approach to the atypical anxiolytic and antidepressant drugs opipramol (Ensidon) and phenelzine (Nardil) by performing lipolysis assays on other sets of adipocyte preparations. Our working hypothesis was that opipramol, which is an iminostilbene derivative, would not exhibit any deleterious effect on lipolysis because it is not recognized for causing weight gain in patients [23], and that phenelzine could be potentially lipolytic because we recently reported that this MAO inhibitor limits fat accumulation in rodents [8,9,25], a finding observed with selegiline, another MAO inhibitor [26].…”

Section: Influence Of Opipramol On Basal and Stimulated Lipolytic Actmentioning

confidence: 99%

“…Alongside the test of their lipolytic and antilipolytic capacities on freshly isolated adipocytes, we also studied their putative interactions with the amine oxidases expressed in adipocytes. Exploring the effects on monoamine oxidase (MAO) was driven by the similarities between the adipose (mainly of the A form in human adipocytes [24]) and the brain forms, well known to be the target of a class of antidepressants, the MAO inhibitors, which have been recently reported to mitigate excessive fat deposition in rodents [8,9,25,26]. Thus, pargyline, phenelzine, and harmine were used as representatives of MAO inhibitors in both assays of lipolytic or amine oxidation activities.…”

Section: Introductionmentioning

confidence: 99%

Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control

et al. 2020

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Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity.

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Selegiline reduces adiposity induced by high‐fat, high‐sucrose diet in male rats

Cited by 16 publications

References 52 publications

Past, Present and Future Anti-Obesity Effects of Flavin-Containing and/or Copper-Containing Amine Oxidase Inhibitors

Past, Present and Future Anti-Obesity Effects of Flavin-Containing and/or Copper-Containing Amine Oxidase Inhibitors

Monoamine Oxidase-Related Vascular Oxidative Stress in Diseases Associated with Inflammatory Burden

Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control

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