Endothelial cells (ECs) form an active barrier between the circulation and the body. In addition to controlling transport of molecules between these 2 compartments, the endothelium is a major secretory organ, releasing proteins both into the circulation and into the vascular matrix. Although it is clearly important that proteins are correctly sorted into these 2 spaces, we currently know little of the polarization of this secretion or how it is controlled. Here, we present an optimized system for the analysis of polarized secretion and show that it allows the derivation of deep, robust proteomes from small numbers of primary ECs. We present the first endothelial apically and basolaterally secreted proteomes, demonstrating that ECs polarize the secretion of extracellular vesicle cargoes to the apical surface. Conversely, we find that protein secretion at the basolateral surface is focused on components of the extracellular matrix (ECM). Finally, we examine the role of liprin‐α1 in secretion toward the basolateral compartment and identify a subset of ECM components that share this route with fibronectin.—Wei, H., Sundararaman, A., Dickson, E., Rennie‐Campbell, L., Cross, E., Heesom, K. J., Mellor, H. Characterization of the polarized endothelial secretome. FASEB J. 33, 12277‐12287 (2019). http://www.fasebj.org

The liver is a key metabolic organ that undertakes a multitude of physiological processes over the course of a day, including intrahepatic lipid and glucose metabolism which plays a key role in the regulation of systemic lipid and glucose concentrations. It serves as an intermediary organ between exogenous (dietary) and endogenous energy supply to extrahepatic organs. Thus, perturbations in hepatic metabolism can impact widely on metabolic disease risk. For example, the accumulation of intra-hepatocellular TAG (IHTG), for which adiposity is almost invariably a causative factor may result in dysregulation of metabolic pathways. Accumulation of IHTG is likely due to an imbalance between fatty acid delivery, synthesis and removal (via oxidation or export as TAG) from the liver; insulin plays a key role in all of these processes.

Purpose of reviewDe novo lipogenesis (DNL) is a metabolic process occurring mainly within the liver, in humans. Insulin is a primary signal for promoting DNL; thus, nutritional state is a key determinant for upregulation of the pathway. However, the effects of dietary macronutrient composition on hepatic DNL remain unclear. Nor is it clear if a nutrition-induced increase in DNL results in accumulation of intra-hepatic triglyceride (IHTG); a mechanism often proposed for pathological IHTG. Here, we review the latest evidence surrounding the nutritional regulation of hepatic DNL.Recent findingsThe role of carbohydrate intake on hepatic DNL regulation has been well studied, with only limited data on the effects of fats and proteins. Overall, increasing carbohydrate intake typically results in an upregulation of DNL, with fructose being more lipogenic than glucose. For fat, it appears that an increased intake of n-3 polyunsaturated fatty acids downregulates DNL, whilst, in contrast, an increased dietary protein intake may upregulate DNL.SummaryAlthough DNL is upregulated with high-carbohydrate or mixed-macronutrient meal consumption, the effects of fat and protein remain unclear. Additionally, the effects of different phenotypes (including sex, age, ethnicity, and menopause status) in combination with different diets (enriched in different macronutrients) on hepatic DNL requires elucidation.