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

Abstract

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 PPARγ 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 PPARγ and Se together as a powerful combination during the treatment of two associated diseases; obesity and depression.PPARγ 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 PPARγ 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 (TNFα) participate in the progression of depression. They are also obesity-associated parameters. Due to TNFα induced depressive-like behaviors and the positive association between this proinflammatory cytokine and obesity, TNFα-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. PPARγ 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 PPARγ action. Se supplementation or fortification as well as the development of the partial agonists of PPARγ 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.