Chronic consumption of imbalance diets high in sucrose or fat induces abdominal obesity with different pattern of metabolic disturbances and lost in Langerhans cells population.

AIM: Obesity is a worldwide health issue, associated with development of type 2 Diabetes Mellitus. The aim of this study is to analyze the effect of consumption of two hypercaloric diets on metabolic disturbance and beta cells damage. MAIN METHODS: Male Wistar rats were subjected to twelve months consumption of three diets: a Control balanced diet (CTD, carbohydrates 58 %, proteins 29 %, lipids 13 %) and two hypercaloric diets, high in sucrose (HSD, carbohydrates 68 %, proteins 22 %, lipids 10 %) or high in fat (HFD, carbohydrates 31 %, proteins 14 %, lipids 55 %). Serum levels of glucose, triglycerides and free fatty acids were measured after zoometric parameters determination. Antioxidant enzymes activity and oxidative stress-marker were measured in pancreas tissue among histological analysis of Langerhans islets. KEY FINDINGS: Although diets were hypercaloric, the amount of food consumed by rats decreased, resulting in an equal caloric consumption. The HSD induced hypertriglyceridemia and hyperglycemia with higher levels in free fatty acids (FFA, lipotoxicity); whereas HFD did not increased neither the triglycerides nor FFA, nevertheless the loss of islets' cell was larger. Both diets induced obesity with hyperglycemia and significant reduction in Langerhans islets size. SIGNIFICANCE: Our results demonstrate that consumption of HSD induces more significant metabolic disturbances that HFD, although both generated pancreas damage; as well hypercaloric diet consumption is not indispensable to becoming obese; the chronic consumption of unbalanced diets (rich in carbohydrates or lipids) may lead to abdominal obesity with metabolic and functional disturbances, although the total amount of calories are similar.

The high-risk HPV E6 proteins modify the activity of the eIF4E protein via the MEK/ERK and AKT/PKB pathways.

Previous studies have proposed that the human papillomavirus (HPV) E6 oncoproteins modify the transcriptional activity of eIF4E through mechanisms dependent on p53 degradation. However, the effect of these oncoproteins on pathways regulating the activity of the eIF4E protein remains poorly understood. Hence, we investigated the mechanisms whereby E6 proteins regulate the activity of the eIF4E protein and its effect on target genes. Overexpression of E6 constructs (HPV-6, HPV-16, HPV-18, and HPV52) showed that E6 oncoproteins increased phosphorylation of the eIF4E protein (Serine-209). This result was mainly mediated by phosphorylation of the 4EBP1 protein via the PI3K/AKT pathway. Additionally, the pharmacological inhibition of eIF4E phosphorylation in cervical cancer cell lines substantially reduced the protein levels of CCND1 and ODC1, indicating that E6 of the high-risk genotypes may modify protein synthesis of the eIF4E target genes by increasing the activity of the AKT and ERK pathways.

Oxidative stress activates the transcription factors FoxO 1a and FoxO 3a in the hippocampus of rats exposed to low doses of ozone.

The exposure to low doses of ozone induces an oxidative stress state, which is involved in neurodegenerative diseases. Forkhead box O (FoxO) family of transcription factors are activated by oxidative signals and regulate cell proliferation and resistance to oxidative stress. Our aim was to study the effect of chronic exposure to ozone on the activation of FoxO 1a and FoxO 3a in the hippocampus of rats. Male Wistar rats were divided into six groups and exposed to 0.25 ppm of ozone for 0, 7, 15, 30, 60, and 90 days. After treatment, the groups were processed for western blotting and immunohistochemistry against FoxO 3a, Mn SOD, cyclin D2, FoxO 1a, and active caspase 3. We found that exposure to ozone increased the activation of FoxO 3a at 30 and 60 days and expression of Mn SOD at all treatment times. Additionally, increases in cyclin D2 from 7 to 90 days; FoxO 1a at 15, 30, and 60 days; and activate caspase 3 from 30 to 60 days of exposure were noted. The results indicate that ozone alters regulatory pathways related to both the antioxidant system and the cell cycle, inducing neuronal reentry into the cell cycle and apoptotic death.

Bax induces cytochrome c release by multiple mechanisms in mitochondria from MCF7 cells.

Bax, a pro-apoptotic member of the Bcl-2 family of proteins has the ability to form transmembrane pores large enough to allow cytochrome c (Cyt c) release, as well as to activate the mitochondrial permeability transition pore (mPTP); however, no differential study has been conducted to clarify which one of these mechanisms predominates over the other in the same system. In the present study, we treated isolated mitochondria from MCF7 cells with recombinant protein Bax and tested the efficacy of the mPTP inhibitor cyclosporin A (CsA) and of the Bax channel blocker (Bcb) to inhibit cytochrome c release. We also, induced apoptosis in MCF7 cell cultures with TNF-α plus cycloheximide to determine the effect of such compounds in apoptosis induction via mPTP or Bax oligomerization. Cytochrome c release was totally prevented by CsA and partially by Bcb when apoptosis was induced with recombinant Bax in isolated mitochondria from MCF7 cells. CsA increased the number of living cells in cell culture, as compared with the effect of Bax channel blocker. These results indicate that mPTP activation is the predominant pathway for Bax-induced cytochrome c release from MCF7 mitochondria and for apoptosis induction in the whole cell.