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Carpéné C, Les F, Mercader J, et al. Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control. Pharmaceuticals (Basel). 2020;13(3)doi: 10.3390/ph13030041.
Carpéné, C., Les, F., Mercader, J., Gomez-Zorita, S., Grolleau, J. L., Boulet, N., Fontaine, J., Iglesias-Osma, M. C., & Garcia-Barrado, M. J. (2020). Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control. Pharmaceuticals (Basel, Switzerland), 13(3), . https://doi.org/10.3390/ph13030041
Carpéné, Christian, et al. "Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control." Pharmaceuticals (Basel, Switzerland) vol. 13,3 (2020). doi: https://doi.org/10.3390/ph13030041
Carpéné C, Les F, Mercader J, Gomez-Zorita S, Grolleau JL, Boulet N, Fontaine J, Iglesias-Osma MC, Garcia-Barrado MJ. Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control. Pharmaceuticals (Basel). 2020 Mar 05;13(3). doi: 10.3390/ph13030041. PMID: 32151075; PMCID: PMC7151722.
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Pharmaceuticals (Basel). 2020 Mar 05;13(3). doi: 10.3390/ph13030041.

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

Pharmaceuticals (Basel, Switzerland)

Christian Carpéné, Francisco Les, Josep Mercader, Saioa Gomez-Zorita, Jean-Louis Grolleau, Nathalie Boulet, Jessica Fontaine, Mari Carmen Iglesias-Osma, Maria José Garcia-Barrado

Affiliations

  1. Institute of Metabolic and Cardiovascular Diseases, INSERM, UMR1048, Team 1, 31432 Toulouse, France.
  2. I2MC, University of Toulouse, UMR1048, Paul Sabatier University, 31432 Toulouse, France.
  3. Department of Pharmacy, Faculty of Health Sciences, Universidad San Jorge, 50830 Villanueva de Gállego Zaragoza, Spain.
  4. Instituto Agroalimentario de Aragón-IA2, CITA-Universidad de Zaragoza, 50013 Zaragoza, Spain.
  5. Department of Fundamental Biology and Health Sciences, University of the Balearic Islands, 07122 Palma, Spain.
  6. Balearic Islands Health Research Institute (IdISBa), 07120 Palma, Spain.
  7. Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country (UPV/EHU) and Lucio Lascaray Research Institute, 48940 Vitoria, Spain.
  8. Department of Plastic Surgery, CHU Rangueil, 31059 Toulouse, France.
  9. Laboratory of Neuroendocrinology, Institute of Neurosciences of Castilla y León (INCyL), University of Salamanca, 37007 Salamanca, Spain.
  10. Laboratory of Neuroendocrinology and Obesity, Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, 37007 Salamanca, Spain.
  11. Department of Physiology and Pharmacology, Faculty of Medicine, University of Salamanca, 37007 Salamanca, Spain.

PMID: 32151075 PMCID: PMC7151722 DOI: 10.3390/ph13030041

Abstract

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.

Keywords: adipose tissue; antidepressant; antipsychotic; glucose transport; harmine; insulin; lipotoxicity; monoamine oxidase; obesity; opipramol; phenelzine; semicarbazide-sensitive amine oxidase

Conflict of interest statement

The authors declare that they have no conflict of interest for any aspect of this research.

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