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Chronic serotonin reuptake inhibition uncouples brown fat mitochondria and induces beiging/browning process of white fat in overfed rats. | LitMetric

Chronic serotonin reuptake inhibition uncouples brown fat mitochondria and induces beiging/browning process of white fat in overfed rats.

Life Sci

Neuropsyquiatry and Behavior Science Graduate Program, Federal University of Pernambuco-UFPE, Recife, Pernambuco, Brazil; Biochemistry and Physiology Graduate Program, Federal University of Pernambuco-UFPE, Recife, Pernambuco, Brazil; Laboratory of Biochemistry and Exercise Biochemistry, Department of Physical Education and Sports Science, Federal University of Pernambuco-UFPE, Academic Center of Vitória-CAV, Vitória de Santo Antão, Pernambuco, Brazil. Electronic address:

Published: March 2020

AI Article Synopsis

Article Abstract

Aim: To investigate whether a chronic 5-HT reuptake inhibitor (i.e. Fluoxetine-FLX) exposure in young adult rats overfed during suckling period would modulate interscapular brown adipose tissue (iBAT) mitochondria and browning agents in white adipose tissue (WAT).

Methods: Male Wistar rats were assigned into either a normofed group (n = 9 per group) or an overfed group (n = 3 per group) induced by litter size reduction at postnatal day 3 (PND3). Pharmacological manipulation was carried out between PND39 and PND59 and groups were assigned accordingly: Normofed + vehicle solution - NaCl 0.9% (NV group), normofed + FLX solution - 10 mg/kg b.w. (NF group), overfed + vehicle (OV group) and overfed + FLX (OF group). We evaluated mitochondrial oxygen consumption and reactive species (RS) production, oxidative stress analyses (MDA concentration, carbonyl content, REDOX state [GSH/GSSG], global oxy score) in the iBAT, gene (leptin, Ucp1, Sirt1, Pgc1α and Prdm16) and protein (UCP1) expression in the iBAT and epididymal WAT (eWAT).

Key Findings: OV group increased body weight gain, Lee index and oxidative stress in the iBAT. Both FLX-treated groups showed less weight gain compared to their controls. OF group showed different leptin expression in the WAT and iBAT; increased functional UCP1 content and mitochondrial activity with less oxidative stress in the iBAT and upregulation of browning genes in eWAT (Pgc1α, Prdm16 and Ucp1).

Conclusion: Altogether our findings indicated that FLX treatment in young adult overfed animals improved the iBAT mitochondrial function, reduced oxidative stress and induced transcriptional activation of browning agents in white adipose tissue.

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Source
http://dx.doi.org/10.1016/j.lfs.2020.117307DOI Listing

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