No abstract

Obesity is a worldwide individual and public health issue, and contributes to the development of numerous chronic diseases. In particular, maternal obesity has harmful effects on both the mother and child during and after pregnancy. The digestion and metabolism of food are controlled by endocrine factors, including insulin, glucagon and estrogen. These hormonal factors are differentially regulated during pregnancy due to the specialized hormonal environment during this period. In the present study, we examined the effects of 1,25-dihydroxyvitamin D3 (VD3), an active hormonal form of nutritional vitamin D3, on lipid metabolism in pregnant rats. The body weight of rats treated with VD3 was significantly reduced compared to that of the rats in the control group. In addition, histological analysis demonstrated that the amount of fat stored in adipocytes was reduced by treatment with VD3. To determine the role of VD3 in lipid metabolism, the expression levels of lipid metabolism‑associated genes were measured in the rat adipose tissue and liver. VD3 negatively regulated the expression of various lipogenic genes, including fatty acid synthase (FAS), stearoyl-CoA desaturase 1 (SCD1) and acetyl-CoA carboxylase 1 (ACC1), in both the adipose tissue and liver. However, the regulators of lipogenic enzymes such as, sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-γ (PPAR-γ) and insulin-induced gene 2 (INSIG2) were differentially regulated by VD3 in a tissue‑specific manner. On the whole, these findings suggest that VD3 regulates lipid metabolism and deposition in the liver and adipose tissue, and thereby reduces fat in pregnant animals, as well as body weight. Our results suggest that the alteration of lipogenesis through the administration of VD3 may help to reduce excessive weight gain during pregnancy and prevent obesity‑related pregnancy complications such as pre-eclampsia, gestational diabetes, hypertension and issues with labor.

Alzheimer's disease (AD) is closely associated with significant defects in glucose metabolism. To investigate whether AD pathology induced by overexpression of human mutant presenilin 2 (PS2) protein induces changes in glucose metabolism, glucose‑related factors were analyzed in the brain of 12‑month‑old neuron‑specific enolase (NSE)/hPS2m transgenic (Tg) mice. NSE/hPS2m Tg mice used in this study showed AD‑like phenotypes such as the accumulation of Aβ‑42, the increase of γ‑secretase activity and Tau hyperphosphorylation. A significant increase of glucose levels accompanied by a decrease of insulin levels was detected in NSE/hPS2m Tg mice, while the expression levels of insulin receptors were significantly decreased in NSE/hPS2m Tg mice compared to the non‑Tg littermates without affecting the insulin‑like growth factor (IGF) receptor. Moreover, the levels of AKT phosphorylation involved in the downregulation of the insulin receptor signaling pathway were reduced in the brain of NSE/hPS2m Tg mice compared with non‑Tg littermate, although the levels of glycogen synthase kinase 3 (GSK‑3) β phosphorylation were higher in the NSE/hPS2m Tg mice compared to non-Tg littermates. Furthermore, the levels of the expression of Glut‑1 and ‑3 were significantly reduced in the NSE/hPS2m Tg mice compared to those of control mice without affecting the Glut‑4 protein expression between the two groups of mice. In particular, the levels of the Aβ‑42 peptide in the brain of insulin‑treated NSE/hPS2m Tg mice were found to be slightly lower compared with those of the Aβ‑42 peptide in the non‑treated PS2 transgenic mice. Thus, the data presented in this study provide strong evidence that key factors of glucose metabolism are closely associated with the AD pathology induced by the hPS2m protein, and that insulin can serve as a potential therapeutic for AD patients.

The hyperphosphorylation of the protein tau disrupts its normal function on regulating axonal transport and leads to the accumulation of neurofibrillary tangles (NFT), which are involved in the pathogenesis of Alzheimer's disease (AD). This study was performed to investigate whether sodium selenite may inhibit the hyperphosphorylation of tau induced by treatment with tumor necrosis factor‑α (TNF‑α). For this purpose, we studied the changes in cell viability, tau phosphorylation and activity of tau kinases in TNF‑α+selenite-treated neuroblastoma cells. Cell viability was significantly recovered in the group cotreated with TNF‑α and 5 µM selenite for 24 h, but not in the groups treated with TNF‑α and lower concentrations of selenite. Tau phosphorylation was significantly higher in the group treated with TNF‑α+vehicle (instead of selenite) compared to the non‑treated group. However, in the TNF‑α+selenite‑treated group, the total phosphorylation level of tau protein at the Ser404 site was significantly reduced compared to the TNF‑α+vehicle group, although western blot analysis revealed one band of increased intensity in the p‑tau sample, corresponding to a phosphorylated tau isoform of 65‑70 kDa. In addition, sodium selenite treatment led to a significant recovery in the immunofluorescence intensity of the p‑tau protein in the cytoplasm and nucleus and in the apoptotic rate of neuroblastoma cells stained with the p‑tau antibody and 4',6‑diamidino‑2‑phenylindole (DAPI). The phosphorylation of two protein kinases responsible for phosphorylation of tau, glycogen synthase kinase 3β (GSK‑3β) and Akt, also known as protein kinase B, was markedly decreased in the TNF‑α+selenite‑treated group relative to the TNF‑α+vehicle‑treated group. Overall, these results provide strong evidence that sodium selenite (selenium) can inhibit cell death and tau phosphorylation induced by TNF‑α in neuroblastoma cells, through the inhibition GSK‑3β and Akt phosphorylation.