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 1α, 1β, and 6 and tumor necrosis factor-α, 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.