DPP4 Gene DNA Methylation in the Omentum is Associated With Its Gene Expression and Plasma Lipid Profile in Severe Obesity

Severely obese subjects with the metabolic syndrome (MS) have higher dipeptidyl peptidase‐4 (DPP4) expression in their visceral adipose tissue (VAT) compared to obese individuals without MS. We tested the hypothesis that methylation level of CpG sites in the DPP4 promoter CpG island in VAT was genotype‐dependent and associated with DPP4 mRNA abundance and MS‐related phenotypes. The VAT DNA was extracted in 92 severely obese premenopausal women undergoing biliopancreatic derivation for the treatment of obesity. Women were nondiabetic and none of them used medication to treat MS features. Cytosine methylation rates (%) of 102 CpG sites in the DPP4 CpG island were assessed by pyrosequencing of sodium bisulfite‐treated DNA. Methylation rates were >10% for CpG sites 94–102. Their mean methylation rate (%Meth_94–102) was different between genotypes for DPP4 polymorphisms rs13015258 (P = 0.001), rs17848915 (P = 0.0004), and c.1926 G>A (P = 0.001). The %Meth_94–102 correlated negatively with DPP4 mRNA abundance (r = ?0.25, P < 0.05) and positively with plasma high‐density lipoprotein (HDL) cholesterol concentrations (r = 0.22, P < 0.05), whereas DPP4 mRNA abundance correlated positively with plasma total‐/HDL‐cholesterol ratio (r = 0.25; P < 0.05). In the VAT of nondiabetic severely obese women, genotype‐dependent methylation levels of specific CpG sites in the DPP4 promoter CpG island were associated with DPP4 gene expression and variability in the plasma lipid profile. Higher DPP4 gene expression in VAT and its relationship with the plasma lipid profile may be explained by actually unknown DPP4 biological effect or, to another extent, may also be a marker of VAT inflammation known to be associated with metabolic disturbances.     

Conformational and orientation studies of artificial ion channels incorporated into lipid bilayers

The conformational and orientation studies in lipid bilayers of 21 amino acid peptides bearing six crown ethers are reported. The compounds were designed to form artificial ion channels by stacking the crown rings, and were shown to be functional in bilayer membranes. We used Fourier transform infrared spectroscopy and CD spectropolarimetry to study the conformation of the peptides in solution and in lipid bilayers. These studies revealed that hexacrown peptides retain their alpha-helical conformation when incorporated in a lipid bilayer environment. Attenuated total reflectance spectroscopy was used to investigate the orientation of the peptides in a lipid bilayer. Results demonstrated that the peptides are not oriented at a fixed angle in membrane, but rather are in incorporation equilibrium between an active state parallel to the lipid chain and an inactive state adsorbed at the surface of the bilayer. From these results, we propose a model for the channel activity and the gating mechanism of these hexacrown peptides in bilayer membranes.     

On the canopy structure manipulation to buffer climate change effects on insect herbivore development

Insect pest development is often linearly related to air temperature, without taking into account the multiple interactions between the particular host plant and pest, the microclimatic conditions actually experienced by the insect, and the non-linear response of insect development rate to temperature. In this study, using an integrative biophysical model, we have investigated effects of both climatic and tree structure changes on the development of a phytophagous leaf mining moth (Phyllonorycter blancardella), taking into account the heterogeneous microclimatic conditions provided by its host plant, the domestic apple (Malus domestica), the larval body temperature rather than the ambient air temperature, and a non-linear development rate model. Hourly body temperature dynamics of larvae homogeneously dispersed in tree canopies were simulated from hourly meteorological conditions (medium IPCC climate change scenario) within the canopy of apple trees. To analyse the effect of tree architecture on leaf miner development, both pruned and unpruned trees, and one, two and three scaffold branched trees were used. Body temperature dynamics was used to compute larval development time and mortality following the non-linear developmental model for this insect. The results showed that tree pruning influences significantly larval development time and mortality. Nevertheless, the effects of manipulating tree structure on larval development and survival were relatively weak compared with the impact of chosen climate variations. This survey also showed that the variability in insect development time within a year and insect mortality change markedly with climatic variations, and highlights the importance of using non-linear rate curves and insect body temperatures instead of air temperature in forecasting models of climate-related insect pest outbreaks.