Fluoxetine induces lean phenotype in rat by increasing the brown/white adipose tissue ratio and UCP1 expression

The serotonergic system plays a crucial role in the energy balance regulation. Energy balance is mediated by food intake and caloric expenditure. Thus, the present study investigated the mechanisms that might be associated with fluoxetine treatment-induced weight reduction. Wistar male rat pups rece...

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Bibliographic Details
Published in:Journal of bioenergetics and biomembranes 2015-08, Vol.47 (4), p.309-318
Main Authors: da Silva, A. I., Braz, G. R. F., Pedroza, A. A., Nascimento, L., Freitas, C. M., Ferreira, D. J. S., Manhães de Castro, R., Lagranha, C. J.
Format: Article
Language:English
Subjects:
Adipose Tissue, Brown - metabolism
Adipose Tissue, White - metabolism
Animal Anatomy
Animal Biochemistry
Animals
Antidepressants
Biochemistry
Bioenergetics
Bioorganic Chemistry
Body fat
Chemistry
Chemistry and Materials Science
Energy Metabolism - drug effects
Fluoxetine - pharmacology
Gene Expression Regulation - drug effects
Histology
Ion Channels - biosynthesis
Male
Mitochondria
Mitochondrial Proteins - biosynthesis
Morphology
Organic Chemistry
Protein expression
Rats
Rats, Wistar
Reactive Oxygen Species - metabolism
Rodents
Uncoupling Protein 1
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Summary:The serotonergic system plays a crucial role in the energy balance regulation. Energy balance is mediated by food intake and caloric expenditure. Thus, the present study investigated the mechanisms that might be associated with fluoxetine treatment-induced weight reduction. Wistar male rat pups received daily injections with subcutaneous fluoxetine (Fx-group) or vehicle solution (Ct-group) from day 1 until 21 days of age. Several analyses were conducted to verify the involvement of mitochondria in weight reduction. We found that body weight in the Fx-group was lower compared to control. In association to lower fat mass in the Fx-group (25 %). Neither neonatal caloric intake nor food intake reveals significant differences. Evaluating caloric expenditure (locomotor activity and temperature after stimulus), we did not observe differences in locomotor activity. However, we observed that the Fx group had a higher capacity to maintain body temperature in a cold environment compared with the Ct-group. Since brown adipose tissue-(BAT) is specialized for heat production and the rate of heat production is related to mitochondrial function, we found that Fx-treatment increases respiration by 36 %, although after addition of GDP respiration returned to Ct-levels. Examining ROS production we observe that Fx-group produced less ROS than control group. Evaluating uncoupling protein (UCP) expression we found that Fx-treatment increases the expression by 23 %. Taken together, our results suggest that modulation of serotonin system results in positive modulation of UCP and mitochondrial bioenergetics in brown fat tissue.
ISSN:0145-479X
1573-6881
DOI:10.1007/s10863-015-9617-9