Faculty Bibliography

Excess dietary lipid uptake causes obesity, a major global health problem. Enterocyte-absorbed lipids are packaged into chylomicrons, which enter the bloodstream through intestinal lymphatic vessels called lacteals. Here, we show that preventing lacteal chylomicron uptake by inducible endothelial genetic deletion of Neuropilin1 (Nrp1) and Vascular endothelial growth factor receptor 1 (Vegfr1; also known as Flt1) renders mice resistant to diet-induced obesity. Absence of NRP1 and FLT1 receptors increased VEGF-A bioavailability and signaling through VEGFR2, inducing lacteal junction zippering and chylomicron malabsorption. Restoring permeable lacteal junctions by VEGFR2 and vascular endothelial (VE)-cadherin signaling inhibition rescued chylomicron transport in the mutant mice. Zippering of lacteal junctions by disassembly of cytoskeletal VE-cadherin anchors prevented chylomicron uptake in wild-type mice. These data suggest that lacteal junctions may be targets for preventing dietary fat uptake.

RNA plays a central role in gene expression from its transcription in the nucleus through translation and degradation in the cytoplasm. Technological advances in fluorescent microscopy and labeling methodologies have made it possible to detect single molecules of RNA in both fixed and living cells. Here, we focus on the recent developments in RNA imaging that have allowed quantitatively measuring the lives of individual transcripts from birth to death and all the events in between in single cells and tissues. Direct observation of RNAs within their native cellular environment has revealed a complex layer of spatial and temporal regulation that has profoundly impacted our understanding of RNA biology.

OBJECTIVES AND STUDY:This study aimed at measuring the effect in normal to restricted protein diets with specific 15N natural isotopic abundance (NIA) given during gestation and/or lactation on the 15N NIA of fur, liver and muscle in dams and their offspring from birth to adulthood. The secondary aim was to study the effect of growth on the same parameters. METHODS:Female Balb/c mice were fed normal protein diet containing 22% protein or isocaloric low protein diet containing 10% protein throughout gestation. Dam's diets were either maintained or switched to the other diet until weaning at 30 days. All animals were fed standard chow thereafter. Offspring were sacrificed at 1, 11, 30, 60, 480 days and a group of dams at d1. Growth was modeled as an exponential function on the group followed up until 480 days. Fur, liver and muscle were sampled at sacrifice and analyzed for bulk 15N NIA. Fixed effects and interactions between fixed effects and random elements were tested by three-way ANOVA. RESULTS:Higher 15N NIA in the diet resulted in higher organ 15N NIA. Switching from one diet to another changed 15N NIA in each organ. Although dam and offspring shared the same isotopic environment during gestation, 15N NIA at day 1 was higher in dams. Growth rate did not differ between groups after 10 days and decreased between 1 and 5 months. 15N NIA differed between organs and was affected by growth and gestation/lactation. CONCLUSION:Dietary 15N NIA is a major determinant of the 15N NIA of organs. 15N NIA depended on organ and age (i.e. growth) suggesting an effect of metabolism and/or dilution space. Post-natal normal-protein diet of lactating dams could reverse the effect of a protein-restricted diet during gestation on the offspring growth. Measuring 15N NIA in various matrices may open a field of application particularly useful in studying the pre- and post-natal origins of health and disease.