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

Csilla Terézia Nagy, Gábor Koncsos, Zoltán V. Varga, Tamás Baranyai, Sebestyén Tuza, Ferenc Kassai, Aliz Judit Ernyey, István Gyertyán, Kornél Király, A. Oláh, T. Radovits, B. Merkely, Nóra Bukosza, G. Szénási, P. Hamar, Domokos Mathé, Krisztián Szigeti, Csilla Pelyhe, Marek Jelemenský, Zsófia Onódi & 4 others Z. Helyes, Rainer Schulz, Z. Giricz, Péter Ferdinandy

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)3713-3726
Number of pages14
JournalBritish Journal of Pharmacology
Volume175
Issue number18
DOIs
Publication statusPublished - Sep 1 2018

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Selegiline
Adiposity
High Fat Diet
Sucrose
Adipose Tissue
Monoamine Oxidase Inhibitors
Body Weight
Insulin
Diet
Glucose
Homeostasis
Obesity
Fats
Intra-Abdominal Fat
Facilitative Glucose Transport Proteins
Subcutaneous Fat
Monoamine Oxidase
Glucose Tolerance Test
Chemokines
Energy Metabolism

ASJC Scopus subject areas

  • Pharmacology

Cite this

Nagy, C. T., Koncsos, G., Varga, Z. V., Baranyai, T., Tuza, S., Kassai, F., ... Ferdinandy, P. (2018). Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats. British Journal of Pharmacology, 175(18), 3713-3726. https://doi.org/10.1111/bph.14437

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, Aliz Judit; Gyertyán, István; Király, Kornél; Oláh, A.; Radovits, T.; Merkely, B.; Bukosza, Nóra; Szénási, G.; Hamar, P.; Mathé, Domokos; Szigeti, Krisztián; Pelyhe, Csilla; Jelemenský, Marek; Onódi, Zsófia; Helyes, Z.; Schulz, Rainer; Giricz, Z.; Ferdinandy, Péter.

In: British Journal of Pharmacology, Vol. 175, No. 18, 01.09.2018, p. 3713-3726.

Research output: Contribution to journalArticle

Nagy, CT, Koncsos, G, Varga, ZV, Baranyai, T, Tuza, S, Kassai, F, Ernyey, AJ, Gyertyán, I, Király, K, Oláh, A, Radovits, T, Merkely, B, Bukosza, N, Szénási, G, Hamar, P, Mathé, D, Szigeti, K, Pelyhe, C, Jelemenský, M, Onódi, Z, Helyes, Z, Schulz, R, Giricz, Z & Ferdinandy, P 2018, 'Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats', British Journal of Pharmacology, vol. 175, no. 18, pp. 3713-3726. https://doi.org/10.1111/bph.14437
Nagy CT, Koncsos G, Varga ZV, Baranyai T, Tuza S, Kassai F et al. Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats. British Journal of Pharmacology. 2018 Sep 1;175(18):3713-3726. https://doi.org/10.1111/bph.14437
Nagy, Csilla Terézia ; Koncsos, Gábor ; Varga, Zoltán V. ; Baranyai, Tamás ; Tuza, Sebestyén ; Kassai, Ferenc ; Ernyey, Aliz Judit ; Gyertyán, István ; Király, Kornél ; Oláh, A. ; Radovits, T. ; Merkely, B. ; Bukosza, Nóra ; Szénási, G. ; Hamar, P. ; Mathé, Domokos ; Szigeti, Krisztián ; Pelyhe, Csilla ; Jelemenský, Marek ; Onódi, Zsófia ; Helyes, Z. ; Schulz, Rainer ; Giricz, Z. ; Ferdinandy, Péter. / Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats. In: British Journal of Pharmacology. 2018 ; Vol. 175, No. 18. pp. 3713-3726.
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T1 - Selegiline reduces adiposity induced by high-fat, high-sucrose diet in male rats

AU - Nagy, Csilla Terézia

AU - Koncsos, Gábor

AU - Varga, Zoltán V.

AU - Baranyai, Tamás

AU - Tuza, Sebestyén

AU - Kassai, Ferenc

AU - Ernyey, Aliz Judit

AU - Gyertyán, István

AU - Király, Kornél

AU - Oláh, A.

AU - Radovits, T.

AU - Merkely, B.

AU - Bukosza, Nóra

AU - Szénási, G.

AU - Hamar, P.

AU - Mathé, Domokos

AU - Szigeti, Krisztián

AU - Pelyhe, Csilla

AU - Jelemenský, Marek

AU - Onódi, Zsófia

AU - Helyes, Z.

AU - Schulz, Rainer

AU - Giricz, Z.

AU - Ferdinandy, Péter

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N2 - 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.

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