Uncontrolled diabetes results in several metabolic alterations including hyperglycemia. Indeed, several preclinical and clinical studies have suggested that this condition may induce susceptibility and the development of more aggressive infectious diseases, especially those caused by some bacteria (including Chlamydophila pneumoniae, Haemophilus influenzae, and Streptococcus pneumoniae, among others) and viruses [such as coronavirus 2 (CoV2), Influenza A virus, Hepatitis B, etc.]. Although the precise mechanisms that link glycemia to the exacerbated infections remain elusive, hyperglycemia is known to induce a wide array of changes in the immune system activity, including alterations in: (i) the microenvironment of immune cells (e.g., pH, blood viscosity and other biochemical parameters); (ii) the supply of energy to infectious bacteria; (iii) the inflammatory response; and (iv) oxidative stress as a result of bacterial proliferative metabolism. Consistent with this evidence, some bacterial infections are typical (and/or have a worse prognosis) in patients with hypercaloric diets and a stressful lifestyle (conditions that promote hyperglycemic episodes). On this basis, the present review is particularly focused on: (i) the role of diabetes in the development of some bacterial and viral infections by analyzing preclinical and clinical findings; (ii) discussing the possible mechanisms by which hyperglycemia may increase the susceptibility for developing infections; and (iii) further understanding the impact of hyperglycemia on the immune system.

Understanding the regulatory mechanisms that affect obesogenic genes expression in newborns is essential for early prevention efforts, but they remain unclear. Our study aimed to explore whether the maternal p-BMI and GWG were associated with regulatory single-locus DNA methylation in selected obesogenic genes. For this purpose, DNA methylation was assayed by Methylation-Sensitive High Resolution Melting (MS-HRM) technique and Sanger allele-bisulfite sequencing in fifty samples of umbilical vein to evaluate glucosamine-6-phosphate deaminase 2 (GNPDA2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), and leptin receptor (LEPR) genes. Correlations between DNA methylation levels and indicators of maternal nutritional status were carried out. Western blotting was used to evaluate protein expression in extracts of the same samples. Results indicated that GNPDA2 and PGC1α genes have the same level of DNA methylation in all samples; however, a differential DNA methylation of LEPR gene promoter was found, correlating it with GWG and this correlation is unaffected by maternal age or unhealthy habits. Furthermore, leptin receptor (Lep-Rb) was upregulated in samples that showed the lowest levels of DNA methylation. This study highlights the association between poor GWG and adjustments on obesogenic genes expression in newborn tissues with potential consequences for development of obesity in the future.

Metabolic disturbances and systemic pro-inflammatory changes have been reported in children with obesity. However, it is unclear the time-sequence of metabolic or inflammatory modifications during children obesity evolution. Our study aimed to quantify simultaneously metabolomic and inflammatory biomarkers in serum from children with different levels of adiposity. For this purpose, a cross-sectional study was used to perform targeted metabolomics and inflammatory cytokines measurements. Serum samples from children between six to ten years old were analyzed using either body mass index (BMI) or waist-to-height ratio (WHtR) classifications. One hundred and sixty-eight school-aged children were included. BMI classification in children with overweight or obesity showed altered concentrations of glucose and amino acids (glycine and tyrosine). Children classified by WHtR exhibited imbalances in amino acids (glycine, valine, and tyrosine) and lipids (triacyl glycerides and low-density lipoprotein) compared to control group. No differences in systemic inflammation biomarkers or in the prevalence of other results were found in these children. Abnormal arterial blood pressure was found in 32% of children with increased adiposity. In conclusion, obesity in school-aged children is characterized by significant metabolic modifications that are not accompanied by major disturbances in circulating concentrations of inflammatory biomarkers.

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DNA methylation status of RXRα gene promoter has been correlated with maternal diet during early pregnancy, and associated with offspring's adiposity and bone mineral content. In adult life, increased methylation of RXRα promoter region is associated with myocardium pathologies. Early growth response proteins (EGR) are zinc finger transcription factors associated with several cellular pathways such as inflammation, apoptosis, and cardiopathies. DNA-binding sequences of EGR proteins have been reported in the RXRα gene promoter using chromatin immunoprecipitation methods. Here, we used correlations between the maternal pre-pregnancy body mass index (p-BMI), gestational weight gain (GWG), and birth weight (BW) as indirect indicators of the maternal nutritional status as modifier of DNA methylation in the offspring. DNA methylation status from newborns' umbilical vein blood in full-term pregnancy was evaluated in a short sequence (116 pb) of the RXRα gene promoter that contains the elements of response sequence for EGR proteins. Fifty-three bisulfite-modified DNA samples were assessed through methyl-sensitive high-resolution melting (MS-HRM) analysis. To validate the results, we directly sequenced MS-HRM samples to confirm the presence of CpG-methylated positions. In addition, the RXRα protein levels in extracts of umbilical vein blood were evaluated by western blot. We found differential methylation in a specific locus of the RXRα promoter surrounding the EGR-binding sequence; however, no correlation was found with the level of RXRα protein expression. Variability in the methylation status of the RXRα promoter near the EGR transcription factor binding site in newborn cord blood provides controversial epigenetic insights into RXRα regulation via EGR proteins.

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