Dietary fat quality in normolipidic diets affects hepatocyte's nuclear phenotypes

Dietary fat quality affects overall systemic parameters and produce hepatic accumulation of fat and inflammation (steatohepatitis). In this communication we have assessed how mouse liver nuclear phenotypes are influenced by diets containing 7% lipid prepared with lard, linseed oil or soybean oil for 32 weeks. Liver specimens were imprinted on glass slides, fixed and stained with DAPI. 3D confocal images were obtained and employed for the calculation of nuclear thickness, nuclear volume and DAPI-DNA intensity. Hepatocytes’ nuclei could be classified as diploid A, diploid B, tetraploid and higher ploidy levels. Linseed oil in the diet resulted in increased frequency of diploid A (more compact) and less polyploidy, while lard caused increased volume and more polyploidy. Soybean oil produced intermediate nuclear sizes. The results suggest a high demand on liver physiology promoted by lard, which has a predominance of saturated fatty acids, while linseed oil promoted the opposite effect1314CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP465699/2014-62009/16150-6; 2014/50938-

Genetic and Metabolic Determinants of Atrial Fibrillation in a General Population Sample : The CHRIS Study

Atrial fibrillation (AF) is a supraventricular arrhythmia deriving from uncoordinated electrical activation with considerable associated morbidity and mortality. To expand the limited understanding of AF biological mechanisms, we performed two screenings, investigating the genetic and metabolic determinants of AF in the Cooperative Health Research in South Tyrol study. We found 110 AF cases out of 10,509 general population individuals. A genome-wide association scan (GWAS) identified two novel loci (p-value &lt; 5 x 10(-8)) around SNPs rs745582874, next to gene PBX1, and rs768476991, within gene PCCA, with genotype calling confirmed by Sanger sequencing. Risk alleles at both SNPs were enriched in a family detected through familial aggregation analysis of the phenotype, and both rare alleles co-segregated with AF. The metabolic screening of 175 metabolites, in a subset of individuals, revealed a 41% lower concentration of lysophosphatidylcholine lysoPC a C20:3 in AF cases compared to controls (p-adj = 0.005). The genetic findings, combined with previous evidence, indicate that the two identified GWAS loci may be considered novel genetic rare determinants for AF. Considering additionally the association of lysoPC a C20:3 with AF by metabolic screening, our results demonstrate the valuable contribution of the combined genomic and metabolomic approach in studying AF in large-scale population studies.De två första författarna delar förstaförfattarskapet.</p