CLCA2 epigenetic regulation by CTBP1, HDACs, ZEB1, EP300 and miR-196b-5p impacts prostate cancer cell adhesion and EMT in metabolic syndrome disease

Prostate cancer (PCa) is the most common cancer among men. Metabolic syndrome (MeS) is associated with increased PCa aggressiveness and recurrence. Previously, we proposed C-terminal binding protein 1 (CTBP1), a transcriptional co-repressor, as a molecular link between these two conditions. Notably, CTBP1 depletion decreased PCa growth in MeS mice. The aim of this study was to investigate the molecular mechanisms that explain the link between MeS and PCa mediated by CTBP1. We found that CTBP1 repressed chloride channel accessory 2 (CLCA2) expression in prostate xenografts developed in MeS animals. CTBP1 bound to CLCA2 promoter and repressed its transcription and promoter activity in PCa cell lines. Furthermore, we found that CTBP1 formed a repressor complex with ZEB1, EP300 and HDACs that modulates the CLCA2 promoter activity. CLCA2 promoted PCa cell adhesion inhibiting epithelial–mesenchymal transition (EMT) and activating CTNNB1 together with epithelial marker (CDH1) induction, and mesenchymal markers (SNAI2 and TWIST1) repression. Moreover, CLCA2 depletion in PCa cells injected subcutaneously in MeS mice increased the circulating tumor cells foci compared to control. A microRNA (miRNA) expression microarray from PCa xenografts developed in MeS mice, showed 21 miRNAs modulated by CTBP1 involved in angiogenesis, extracellular matrix organization, focal adhesion and adherents junctions, among others. We found that miR-196b-5p directly targets CLCA2 by cloning CLCA2 3′UTR and performing reporter assays. Altogether, we identified a new molecular mechanism to explain PCa and MeS link based on CLCA2 repression by CTBP1 and miR-196b-5p molecules that might act as key factors in the progression onset of this disease.Fil: Porretti, Juliana Carla. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Dalton, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Massillo, Cintia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Scalise, Georgina Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Elble, Randolph. Southern Illinois University; Estados UnidosFil: Gerez, Esther Noemi. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Invest. Sobre Porfirinas y Porfirias. Grupo Vinculado Al Cipyp - Ffyb; ArgentinaFil: Accialini, Paula Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cabanillas, Ana Maria de Los A.. Universidad Nacional de Córdoba; ArgentinaFil: Gardner, Kevin. Columbia University; Estados UnidosFil: de Luca, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentin

Decrease in blood triglycerides associated with the consumption of eggs of hens fed with food supplemented with fish oil

BACKGROUND: n-3 polyunsaturated fatty acids (n-3 PUFA) convey several health benefits, including a reduction of serum concentration of triglycerides (TG). AIM: To examine the effect on blood lipids, particularly TG, of a diet with n-3 PUFA enriched eggs in healthy volunteers in the Seychelles (Indian Ocean). METHODS: Double-blind crossover trial with one group of volunteers fed with 5 normal eggs per week during 3 weeks followed by 5 enriched eggs per week during the next 3 weeks while the other group received eggs in the inverse sequence. Hen feed was supplemented at 5% with tuna oil. Enriched eggs contained nine times more n-3 PUFA than usual eggs (mainly docosahexaenoic acid). RESULTS: Twenty-five healthy volunteers participated in the study. Based on pooled results observed during the two 3-week periods, consumption of enriched eggs was associated with a significant 16-18% decrease in serum triglycerides (P<0.01) but with no significant difference in serum LDL-cholesterol and HDL-cholesterol. Serum LDL-cholesterol increased during the first 3-week period and decreased during the second 3-week period with both normal and enriched eggs. Participants did not report a systematic preference for either type of eggs. CONCLUSIONS: Reasonable consumption of n-3 PUFA enriched eggs was associated with a significant decrease in serum triglycerides. These eggs could be a palatably acceptable source of n-3 PUFA

Low energy and carbohydrate intake associated with higher total antioxidant capacity in apparently healthy adults.

Objectives: The aim of this study was to investigate the associations between plasma total antioxidant capacity (TAC) and anthropometric, biochemical, clinical, and dietary measurements in young and apparently healthy individuals. Methods: We evaluated 156 individuals (91 women and 65 men; ages 23.1 _ 3.5 y; body mass index 22 _ 2.9 kg/m2) for anthropometrics, biochemical markers, clinical, dietary, and some components of the antioxidant defense system, including the plasma TAC. Statistical analyses were performed to detect differences between individuals with TAC higher and lower than the mean value and to screen the associations between TAC and variables of interest. A linear regression model was fitted to identify TAC predictors. Results: Daily caloric intake and macronutrient consumption were lower in individuals who exhibited the highest TAC values (P < 0.05). Linear regression analysis showed that daily calories and carbohydrate intake was a possible negative TAC predictor (P < 0.05). Nevertheless, there was no difference in the values of oxidized low-density lipoprotein in the individuals separated by means of TAC. In contrast, individuals whose plasma TAC values were above the mean showed higher low-density lipoprotein cholesterol concentrations, total cholesterol/high-density lipoprotein cholesterol values, and selenium in nails (P < 0.05). Conclusions: In physiological conditions, the caloric intake level seems to be an important factor to act in the modulation of plasma TAC, before establishing anthropometric impairments of body or metabolic composition, or both. Additionally, the plasma TAC increase may be able to act as a compensatory mechanism

Indian Asians have poorer cardiovascular autonomic function than Europeans: this is due to greater hyperglycaemia and may contribute to their greater risk of heart disease.

Indian Asians from the general population have impaired cardiovascular autonomic function compared with Europeans. This is due to greater hyperglycaemia in Indian Asians and may determine their increased CHD risk