Body fat reduction without cardiovascular changes in mice after oral treatment with the MAO inhibitor phenelzine

Abstract

As phenelzine reduced body fat content without affecting cardiovascular function in mice, it may be of benefit in the treatment of obesity-associated complications, with the precautions of use recommended for antidepressant therapy.

Metabolic Effects of Oral Phenelzine Treatment on High-Sucrose-Drinking Mice

“…Such an effect eventually inhibits adipocyte differentiation, which has been shown in several murine cell lines and in human primary cultures of a stromal vascular fraction derived from adipose tissue and bone marrow mesenchymal stem cells [ 10 , 11 ]. Furthermore, we have recently shown that chronic phenelzine administration reduces body fat accumulation even in normal-weight mice, which was associated to a lower rate of insulin- and benzylamine-stimulated glucose incorporation into lipids in adipocytes [ 12 ]. Fat-reducing effects evidenced in animals and cultured cells contrasts with the weight gain observed in patients with mood disorders treated with this compound [ 13 ].…”

Attenuation of Weight Gain and Prevention of Associated Pathologies by Inhibiting SSAO

“…Phenelzine, which is a derivative of hydrazine, is found to affect adiposity, glucose, insulin, and lipid homeostasis as well as markers of oxidative stress and low-grade inflammation in mice models. It represents a potent inhibitor of MAO and SSAO [40,46,47]. Holoamine 2-bromoethylamine (2-BEA) was also discovered to be a highly selective potential inhibitor of membrane-bound SSAO [30].…”

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

“…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].…”

“…Although the antidepressant phenelzine is recognized as inducing some weight gain in patients, this effect is of lower amplitude than with other antidepressants [41], and this is not supported by any higher activating influence on lipid mobilization when compared to the antipsychotics tested here. Because phenelzine has been reported to modestly limit fat accretion in animal models [8,9,25], this might rather be related to an impairment of lipogenic activity, as reported in mouse fat cells [6]. Because opipramol behaved differently from various other psychoactive substances, at least regarding lipolysis regulation in fat cells, we examined the way in which it interacted with MAO activity and another major amine oxidase expressed in adipose tissue-the semicarbazide-sensitive amine oxidase (SSAO) [43].…”

“…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.…”