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Balearic Islands Health Research Institute, Palma de Mallorca, Spain (J.M.); Department of Fundamental Biology and Health Sciences, University of Balearic Islands (UIB), Palma de Mallorca, Spain (J.M.); Alimentómica, S.L., Spin-off from UIB, Palma de Mallorca, Spain (A.G.S.); Institute of Metabolic and Cardiovascular Diseases, INSERM, UMR1048, Teams 1 & 3, Toulouse, France (C.C., S.L.G., P.D.); I2MC, University of Toulouse, UMR1048, Paul Sabatier University, Toulouse Cedex 4, France (C.C., S.L.G., P.D.); Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cleveland, Ohio (A.C.); Nutrition and Obesity Group, Department of Nutrition and Food Science, University of the Basque Country and Lucio Lascaray Research Institute, Vitoria, Spain (S.G.-Z.); CIBERobn Physiopathology of Obesity and Nutrition, Institute of Health Carlos III, Madrid, Spain (S.G.-Z., F.I.M.); Department of Nutrition, Food Science, and Physiology, University of Navarra, Pamplona, Spain (F.I.M.); and Centre for Nutrition Research, University of Navarra, Pamplona, Spain (F.I.M.)
Published: November 2019
AI Article Synopsis
Article Abstract
Novel mechanisms and health benefits have been recently suggested for the antidepressant drug phenelzine (PHE), known as a nonselective monoamine oxidase inhibitor. They include an antilipogenic action that could have an impact on excessive fat accumulation and obesity-related metabolic alterations. We evaluated the metabolic effects of an oral PHE treatment on mice fed a high-fat diet (HFD). Eleven-week-old male C57BL/6 mice were fed a HFD and either a 0.028% PHE solution (HFD + PHE) or water to drink for 11 weeks. PHE attenuated the increase in body weight and adiposity without affecting food consumption. Energy efficiency was lower in HFD + PHE mice. Lipid content was reduced in subcutaneous fat pads, liver, and skeletal muscle. In white adipose tissue (WAT), PHE reduced sterol regulatory element-binding protein-1c and phosphoenolpyruvate carboxykinase mRNA levels, inhibited amine-induced lipogenesis, and did not increase lipolysis. Moreover, HFD + PHE mice presented diminished levels of hydrogen peroxide release in subcutaneous WAT and reduced expression of leukocyte transmigration markers and proinflammatory cytokines in visceral WAT and liver. PHE reduced the circulating levels of glycerol, triacylglycerols, high-density lipoprotein cholesterol, and insulin. Insulin resistance was reduced, without affecting glucose levels and glucose tolerance. In contrast, PHE increased rectal temperature and slightly increased energy expenditure. The mitigation of HFD-induced metabolic disturbances points toward a promising role for PHE in obesity treatment and encourages further research on its mechanisms of action. SIGNIFICANCE STATEMENT: Phenelzine reduces body fat, markers of oxidative stress, inflammation, and insulin resistance in high-fat diet mice. Semicarbazide-sensitive amine oxidase, monoamine oxidase, phosphoenolpyruvate carboxykinase, and sterol regulatory element-binding protein-1c are involved in the metabolic effects of phenelzine. Phenelzine could be potentially used for the treatment of obesity-related complications.
