Different Effects of Low Selenite and Selenium-Nanoparticle Supplementation on Adipose Tissue Function and Insulin Secretion in Adolescent Male Rats

Abstract

Adolescence is a period of intense growth and endocrine changes, and obesity and insulin-resistance processes during this period have lately been rising. Selenium (Se) homeostasis is related to lipid metabolism depending on the form and dose of Se. This study tests the actions of low-dose selenite and Se nanoparticles (SeNPs) on white (WAT) and brown adipose tissue (BAT) deposition, insulin secretion, and GPx1, IRS-1 and FOXO3a expression in the WAT of adolescent rats as regards oxidative stress, adipocyte length and adipokine secretion. Four groups of male adolescent rats were treated: control (C), low selenite supplementation (S), low SeNP supplementation (NS) and moderate SeNP supplementation (NSS). Supplementation was received orally through water intake; NS and NSS rats received two- and tenfold more Se than C animals, respectively. SeNPs were obtained by reducing Se tetrachloride in the presence of ascorbic acid. For the first time in vivo, it was demonstrated that low selenite supplementation contributed to increased adipogenesis via the insulin signaling pathway and LCN2 modulation, while low SeNP administration prevented fat depots in WAT via the decrease in insulin signaling and FOXO3a autophagy in WAT, lowering inflammation. These effects were independent of GPx1 expression or activity in WAT. These findings provide data for dietary approaches to prevent obesity and/or anorexia during adolescence. These findings may be relevant to future studies looking at a nutritional approach aimed at pre-venting obesity and/or anorexia in adolescence.

Trends and recent progresses of selenium nanoparticles as novel autophagy regulators for therapeutic development

“…In recent years, the ability of Se NPs for autophagy regulation has been proved to show strong potentials in some impotent diseases, including cancer, tuberculosis, rheumatoid arthritis, adolescent obesity or anorexia, skin diseases, diabetes and kidney injury. The attractive bioactivity of Se NPs for autophagy modulation not only suggests Se NPs for disease treatment alone ( 78 , 79 ), but also introduces the possibilities to combine Se NPs and current chemotherapeutics to achieve enhanced efficiency ( 70 , 71 ), which would be beneficial in facilitating the development of new therapies.…”

“…However, there are still lots of critical issues for the further clinical application of Se NPs by regulating autophagy. Firstly, although some works have indicated the potential mechanisms of Se NPs induced autophagy, most of these works just provided some phenotype results without depth investigations ( 68 , 75 , 78 ). To further confirm the detailed mechanisms of Se NPs induced autophagy, knockout/knockdown experiments in cell and mice models are needed.…”

“…Obesity, insulin resistance, and anorexia nervosa are particularly rising during this period. Ojeda et al ( 78 ) firstly demonstrated in vivo that low selenite supplementation could promote adipogenesis through the insulin signaling pathway and lipocalin2 regulation, while low Se NPs administration could prevent fat storage in white adipose tissue and alleviate inflammation by reducing insulin signaling pathway and FOXO3A autophagy. These results provided data for dietary approaches to prevent obesity and/or anorexia during adolescence using Se NPs as autophagy regulators and also highlighted the potential roles of Se NPs for the prevention of adipocyte differentiation.…”

Microbiota-Liver-Bile Salts Axis, a Novel Mechanism Involved in the Contrasting Effects of Sodium Selenite and Selenium-Nanoparticle Supplementation on Adipose Tissue Development in Adolescent Rats

“…Correct oxidative balance is deeply related to the endocrine signaling process and cell proliferation and differentiation [4]. It has been recently found that Se is deeply related to white adipose tissue (WAT) metabolism during adolescence [5]. However, its effects clearly differ depending on the form of administration.…”

“…This treatment decreased insulin signaling and increased forkhead box O3a (FOXO3a), affecting autophagy and lowering inflammation. However, since both forms of Se administration increased the activity of the antioxidant enzyme GPx1 in the same way, it is inferred that their contrasting effects on WAT adipocytes are GPx1-independent [5]. Therefore, there must be additional factors that contribute to these deep changes in lipid homeostasis.…”