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

Abstract

BACKGROUND AND PURPOSE:

Incidence and severity of obesity are increasing worldwide, however, efficient and safe pharmacological treatments are not yet available. Certain MAO inhibitors reduce body weight, although their effects on metabolic parameters have not been investigated. Here, we have assessed effects of a widely used, selective MAO-B inhibitor, selegiline, on metabolic parameters in a rat model of diet-induced obesity.

EXPERIMENTAL APPROACH:

Male Long-Evans rats were given control (CON) or a high-fat (20%), high-sucrose (15%) diet (HFS) for 25 weeks. From week 16, animals were injected s.c. with 0.25 mg·kg-1 selegiline (CON + S and HFS + S) or vehicle (CON, HFS) once daily. Whole body, subcutaneous and visceral fat was measured by CT, and glucose and insulin tolerance were tested. Expression of glucose transporters and chemokines was assessed by quantitative RT-PCR.

KEY RESULTS:

Selegiline decreased whole body fat, subcutaneous- and visceral adiposity, measured by CT and epididymal fat weight in the HFS group, compared with HFS placebo animals, without influencing body weight. Oral glucose tolerance and insulin tolerance tests showed impaired glucose homeostasis in HFS and HFS + S groups, although insulin levels in plasma and pancreas were unchanged. HFS induced expression of Srebp-1c, Glut1 and Ccl3 in adipose tissue, which were alleviated by selegiline.

CONCLUSIONS AND IMPLICATIONS:

Selegiline reduced adiposity, changes in adipose tissue energy metabolism and adipose inflammation induced by HFS diet without affecting the increased body weight, impairment of glucose homeostasis, or behaviour. These results suggest that selegiline could mitigate harmful effects of visceral adiposity.

• Authors: Csilla Terézia Nagy, Gábor Koncsos, Zoltán V Varga, Tamás Baranyai, Sebestyén Tuza, Ferenc Kassai, Aliz Judit Ernyey, István Gyertyán, Kornél Király, Attila Oláh, Tamás Radovits, Béla Merkely, Nóra Bukosza, Gábor Szénási, Péter Hamar, Domokos Mathé, Krisztián Szigeti, Csilla Pelyhe, Marek Jelemenský, Zsófia Onódi, Zsuzsanna Helyes, Rainer Schulz, Zoltán Giricz, Péter Ferdinandy
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 175 Issue 18 Pg. 3713-3726 (09 2018) ISSN: 1476-5381 [Electronic] England
• PMID: 29971762 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The British Pharmacological Society.

Chemical References

• Chemokine CCL3
• Dietary Sucrose
• Glucose Transporter Type 1
• Membrane Proteins
• Monoamine Oxidase Inhibitors
• Ndufa1 protein, mammalian
• Slc2a1 protein, rat
• Srebf1 protein, rat
• Sterol Regulatory Element Binding Protein 1
• Selegiline
• Glucose

Topics

• Adipose Tissue, White (drug effects, metabolism)
• Adiposity (drug effects)
• Animals
• Blood Pressure (drug effects)
• Body Weight (drug effects)
• Chemokine CCL3 (genetics)
• Diet, High-Fat
• Dietary Sucrose (administration & dosage)
• Energy Intake
• Glucose (metabolism)
• Glucose Transporter Type 1 (genetics)
• Lipid Metabolism (drug effects)
• Male
• Membrane Proteins (genetics)
• Monoamine Oxidase Inhibitors (pharmacology)
• Organ Size (drug effects)
• Rats
• Rats, Long-Evans
• Selegiline (pharmacology)
• Sterol Regulatory Element Binding Protein 1 (genetics)
• Systole