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Int J Mol Sci. 2018 Sep 25;19(10). pii: E2904. doi: 10.3390/ijms19102904.

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

Author information

1
INSERM U1048, Institute of Metabolic and Cardiovascular Diseases (I2MC), University Paul Sabatier, 31059 Toulouse, France. christian.carpene@inserm.fr.
2
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. saioa.gomez@ehu.eus.
3
Biomedical Research Networking Centres, Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, 28029 Madrid, Spain. saioa.gomez@ehu.eus.
4
Cardiovascular Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA. amc315@case.edu.
5
Laboratory of Molecular Biology, Nutrition and Biotechnology, University of the Balearic Islands, 07122 Palma, Spain. josep.mercader@uib.es.
6
Balearic Islands Health Research Institute (IdISBa), 07010 Palma, Spain. josep.mercader@uib.es.

Abstract

Phenelzine has been suggested to have an antiobesity effect by inhibiting de novo lipogenesis, which led us to investigate the metabolic effects of oral chronic phenelzine treatment in high-sucrose-drinking mice. Sucrose-drinking mice presented higher body weight gain and adiposity versus controls. Phenelzine addition did not decrease such parameters, even though fat pad lipid content and weights were not different from controls. In visceral adipocytes, phenelzine did not impair insulin-stimulated de novo lipogenesis and had no effect on lipolysis. However, phenelzine reduced the mRNA levels of glucose transporters 1 and 4 and phosphoenolpyruvate carboxykinase in inguinal white adipose tissue (iWAT), and altered circulating levels of free fatty acids (FFA) and glycerol. Interestingly, glycemia was restored in phenelzine-treated mice, which also had higher insulinaemia. Phenelzine-treated mice presented higher rectal temperature, which was associated to reduced mRNA levels of uncoupling protein 1 in brown adipose tissue. Furthermore, unlike sucrose-drinking mice, hepatic malondialdehyde levels were not altered. In conclusion, although de novo lipogenesis was not inhibited by phenelzine, the data suggest that the ability to re-esterify FFA is impaired in iWAT. Moreover, the effects on glucose homeostasis and oxidative stress suggest that phenelzine could alleviate obesity-related alterations and deserves further investigation in obesity models.

KEYWORDS:

adipocyte; amine oxidases; hydrogen peroxide; hyperglycemia; lipogenesis; obesity; oxidative stress; phenelzine

PMID:
30257452
PMCID:
PMC6213466
DOI:
10.3390/ijms19102904
[Indexed for MEDLINE]
Free PMC Article

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