The Endothelium: An Active Regulator of Lipid and Glucose Homeostasis

Endothelial cells (ECs) adjust transport rates of nutrients and hormones in an organ-specific manner. As such, ECs are key metabolic gatekeepers of the organism. Several signaling pathways, transcriptional regulators, and metabolites have recently been identified that regulate endothelial transcytosis of long-chain fatty acids. Manipulation of endothelial fatty acid transport leads to pronounced changes in insulin sensitivity. The endothelium constitutes an organ-specific barrier that regulates the availability of insulin to neurons, myocytes, and adipocytes. Regulated endothelial transport of glucose and docosahexaenoic acid across the blood–brain barrier is essential for maintaining cognitive function. The vascular endothelium serves as a dynamic barrier that separates blood from interstitia. Endothelial cells (ECs) respond rapidly to changes in the circulation and actively regulate vessel tone, permeability, and platelet functions. ECs also secrete angiocrine factors that dictate the function of adjacent parenchymal cells in an organ-specific manner. Endothelial dysfunction is considered as a hallmark of metabolic diseases. However, there is emerging evidence that ECs modulate the transfer of nutrients and hormones to parenchymal cells in response to alterations in metabolic profile. As such, a causal role for ECs in systemic metabolic dysregulation can be envisaged. This review summarizes recent progress in the understanding of regulated fatty acid, glucose, and insulin transport across the endothelium and discusses its pathophysiological implications. The vascular endothelium serves as a dynamic barrier that separates blood from interstitia. Endothelial cells (ECs) respond rapidly to changes in the circulation and actively regulate vessel tone, permeability, and platelet functions. ECs also secrete angiocrine factors that dictate the function of adjacent parenchymal cells in an organ-specific manner. Endothelial dysfunction is considered as a hallmark of metabolic diseases. However, there is emerging evidence that ECs modulate the transfer of nutrients and hormones to parenchymal cells in response to alterations in metabolic profile. As such, a causal role for ECs in systemic metabolic dysregulation can be envisaged. This review summarizes recent progress in the understanding of regulated fatty acid, glucose, and insulin transport across the endothelium and discusses its pathophysiological implications. also known as angiokines, these molecules are secreted from vascular cells and act locally or systemically on parenchymal cells. a highly selective semipermeable border that separates blood from the central nervous system to restrict the passage of pathogens and toxic substances into the cerebrospinal fluid. The BBB is formed by endothelial cells that lack fenestrations, have low pinocytotic activity, and are connected by a dense net of tight junctions. In addition to endothelial cells (ECs), the BBB includes the capillary basement membrane, pericytes, and a sheath of astrocytic foot projections. ultra low density lipoproteins that transport lipids, in particular triglycerides (TAGs), from the intestine to other organs (e.g., muscle and adipose tissue). In enterocytes, TAGs are combined with phospholipids, cholesteryl esters, and apolipoprotein B-48 to form water-soluble particles. The nascent chylomicrons are secreted into lymphatic capillaries (lacteals). a metabolic disorder characterized by elevated blood glucose levels. Type 1 diabetes results from a failure of the pancreas to produce sufficient insulin, usually caused by an autoimmune response against β cells. The much more frequent type 2 diabetes is characterized by insulin resistance. The most important risk factor is the combination of excessive body weight and too little exercise. lack of an adequate oxygen supply. a pathological condition characterized by decreased metabolic action of insulin, particularly leading to impaired glucose uptake by muscle and adipose tissue, and failure to repress gluconeogenesis in liver. a free radical produced mainly in endothelial cells by an NADPH-dependent NO synthase. NO acts as a signaling molecule by activating guanylate cyclases. NO induces vasodilation to increase local blood supply, inhibits platelet aggregation, and reduces leukocyte adhesion to the blood vessel wall. heat production. Non-shivering thermogenesis is induced by sympathetic nervous system and thyroid hormones in brown adipose tissue. Uncoupling of the electron transfer chain at the inner mitochondrial membrane by the protein thermogenin (UCP1) allows the energy of protons to be dissipated as heat.