Obesity Hinders the Protective Effect of Selenite Supplementation on Insulin Signaling

Abstract

The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.

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

“…However, it is not enough since the adipogenesis process is stopped and hyperglycemia further appears. According to these results, in a recent multidisciplinary study, in vivo selenite vs. in vitro selenite supplementation have been found to show different effects on WAT-insulin sensitivity during obesity and highfat diet exposure [78]. In this case, in vitro selenite supplementation protects against IR in 3T3-L1 preadipocytes, despite in vivo studies in mice showing no selenite-induced improvement in insulin sensitivity, with only a modest effect on adipocyte morphology and enhanced insulin production in the pancreas.…”

Uncovering the Role of Selenite and Selenium Nanoparticles (SeNPs) in Adolescent Rat Adipose Tissue beyond Oxidative Balance: Transcriptomic Analysis

“…Curiously, rats supplemented with selenite also showed a positive regulation of one selenoprotein, the GPx3, compared to SeNPs-treated rats (Log 2 FC = 0.80). Recent studies have found that selenite treatment increases GPx3 mRNA and protein levels in a dose-dependent manner, enhancing insulin receptor (IRS-1) expression through the activation of the transcription factor Sp1 in different adipocyte cell culture models [ 43 , 44 ]. This improvement in insulin sensitivity increases the differentiation and function of adipocytes.…”

“…These effects of Se supplementations on WAT main metabolic pathways align with those found in oxidative balance. In this context, selenite treatment, which inhibits lipolysis and enhances growth signaling, upregulated the genes associated to the antioxidant enzyme GPx3, which improves the insulin signaling process contributing to avoid lipolysis [ 44 ]. It also increased the gene which encoded COX-1, an important modulator of growth pathways [ 45 ] and a promoter of adipogenesis [ 46 ].…”