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

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.

Protective effects of estrogen against cardiovascular disease mediated via oxidative stress in the brain.

During their reproductive years women produce significant levels of estrogens, predominantly in the form of estradiol, that are thought to play an important role in cardioprotection. Mechanisms underlying this action include both estrogen-mediated changes in gene expression, and post-transcriptional activation of protein signaling cascades in the heart and in neural centers controlling cardiovascular function, in particular, in the brainstem. There, specific neurons, especially those of the bulbar region play an important role in the neuronal control of the cardiovascular system because they control the outflow of sympathetic activity and parasympathetic activity as well as the reception of chemical and mechanical signals. In the present review, we discuss how estrogens exert their cardioprotective effect in part by modulating the actions of internally generated products of cellular oxidation such as reactive oxygen species (ROS) in brain stem neurons. The significance of this review is in integrating the literature of oxidative damage in the brain with the literature of neuroprotection by estrogen in order to better understand both the benefits and limitations of using this hormone to prevent cardiovascular disease.