Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Effect of dietary glucosylceramide from sea cucumber on plasma and liver lipids in cholesterol-fed mice

Various physiological functions of dietary glucosylceramides (GlcCer) have been reported, such as preventing colon cancer and improving skin barrier function. One potential GlcCer source used as a foodstuff is sea cucumber. In this study, our objective was to determine the effect of dietary GlcCer prepared from sea cucumber on plasma and liver lipids in cholesterol-fed mice. ICR mice were fed four different diets (control diet, sea cucumber GlcCer supplemented diet, high cholesterol supplemented diet, and high cholesterol + sea cucumber GlcCer supplemented diet). Dietary GlcCer decreased total cholesterol significantly in ICR mice. The mRNA expression of LDL receptor was increased significantly, while the expression of the gene CYP7A1, which is involved in bile acid formation, was decreased significantly compared with the control (diet without cholesterol). These results suggest that the expression of the cholesterol homeostasis gene in liver is modulated due to the cholesterol lowering effect of dietary GlcCer

Identification of glucosylceramides containing sphingatrienine in maize and rice using ion trap mass spectrometry.

We characterized the glucosylceramide moieties from maize and rice using liquid chromatography-ion trap mass spectrometry. Glucosylceramides containing 4, 8-sphingadienine (d18:2) acylated to hydroxy-fatty acids were detected as the predominant molecules both in maize and in rice. In addition, 4-hydroxy-8-sphingenine (t18:1) and sphingatrienine (d18:3) were found in maize and rice glucosylceramides, and in the case of rice, sphingenine (d18:1) was also detected. Glucosylceramides containing d18:3 were acylated to hydroxyl fatty acids (16-24 carbon atoms). Our results indicate the presence of the triene type of sphingoid base in higher plants

Oral glucosylceramide reduces 2,4-dinitrofluorobenzene induced inflammatory response in mice by reducing TNF-alpha levels and leukocyte infiltration.

Sphingolipids are constituents of cellular membranes and play important roles as second messengers mediating cell functions. As significant components in foods, sphingolipids have been proven to be critical for human health. Moreover, diverse metabolic intermediates of sphingolipids are known to play key roles both in proinflammatory and in anti-inflammatory effects. However, the effect of dietary sphingolipids on inflammation is a complicated field that needs to be further assessed. Our study evaluated the effects of orally administered maize glucosylceramide (GluCer), one of the most conventional dietary sphingolipids, on inflammation using the 2, 4-dinitro-1-fluorobenzene-treated BALB/c murine model. Oral administration of GluCer inhibited ear swelling and leukocyte infiltration to the inflammatory site, suggesting that dietary GluCer has anti-inflammatory properties. ELISA analyses revealed that oral administration of GluCer for 6 days had not modified the Th1/Th2 balance, but significantly down-regulated the activation of TNF-α at the inflammatory site. Based on these results, the down-regulation of TNF-α by dietary GluCer may suppress vascular permeability and reduce the migration of inflammatory cells. Our findings increase understanding of the actions of dietary sphingolipids on the balance of the immune response