4.5 Article

Promising link between selenium and peroxisome proliferator activated receptor gamma in the treatment protocols of obesity as well as depression

Journal

MEDICAL HYPOTHESES
Volume 89, Issue -, Pages 79-83

Publisher

CHURCHILL LIVINGSTONE
DOI: 10.1016/j.mehy.2016.02.008

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Considerable interest has been given to the significance of peroxisome proliferator activated receptors (PPARs) in macronutrient metabolism, however, there is not sufficient data concerning the interactions between PPARs and micronutrients. Investigations performed on PPAR gamma and one of the essential micronutrients selenium (Se) have shown that both parameters may lead to alterations in obesity related or mood disorders. Therefore, it is plausible to consider PPAR gamma and Se together as a powerful combination during the treatment of two associated diseases; obesity and depression. PPAR gamma has been shown to be involved in the antidepressant-like activity. It is also an important parameter to be considered in obesity as the master regulator of adipogenesis. The mechanism of action of PPAR gamma is initiated by ligand binding which induces a conformational change in the receptor. Se is capable of alleviating inflammatory signaling pathways. Obesity is associated with chronic low-grade inflammation. Depression is also defined as an inflammatory disorder. Inflammatory mediators such as tumor necrosis factor-alpha (TNF alpha) participate in the progression of depression. They are also obesity associated parameters. Due to TNF alpha induced depressive-like behaviors and the positive association between this proinflammatory cytokine and obesity, TNF alpha-activated signaling pathways and those inhibiting them have recently gained importance as potential targets and therapeutic tools, respectively. More studies are necessary to develop compounds with therapeutic nature against depressive disorders and obesity. PPAR gamma is an important signaling pathway that occurs at the crossroads of depression and obesity. Se, aside from its anti-inflammatory, anticarcinogenic and antioxidative nature, affects also the way of PPAR gamma action. Se supplementation or fortification as well as the development of the partial agonists of PPAR gamma in which lipophilic Se compounds are used as ligand followed by experimental trials and human studies using the newly developed compounds will be promising approaches for future hope during the treatment of these diseases. (C) 2016 Elsevier Ltd. All rights reserved.

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