Anorectic effects of circulating cytokines: role of the vascular blood-brain barrier

Communication between the central nervous system and peripheral tissues is mediated in part by the ability of the blood-brain barrier (BBB) to transport peptides and regulatory proteins. Many cytokines with effects on appetite, including interleukins 1alpha, 1beta, and 6 and tumor necrosis factor-alpha, are transported across the BBB. Cytokines also can interact with the luminal surface of the brain endothelial cells, which constitute the BBB, to induce brain endothelial cells to release appetite-affecting substances into brain interstitial fluid. Leptin, a 16-kDa protein that binds to a cytokine receptor, is produced by fat cells and transported across the BBB by a saturable system to exert its anorectic effects. Transporter performance for appetite-related peptides and regulatory proteins can be altered by disease and under conditions associated with anorexia or obesity, a striking example being leptin transport in obesity. In mice with obesity of maturity, leptin transport is reduced by about two-thirds, showing that obesity involves a dysfunction of the BBB. That altered transport across the BBB of other substances related to feeding also might result in obesity or anorexia is a possibility that deserves investigation.