Transgenic expression of syndecan-1 uncovers a physiological control of feeding behavior by syndecan-3

Transgenic expression in the hypothalamus of syndecan-1, a cell surface hep aran sulfate proteoglycan (HSPG) and modulator of ligand-receptor encounter s, produces mice with hyperphagia and maturity-onset obesity resembling mic e with reduced action of alpha melanocyte stimulating hormone (alpha MSH). Via their HS chains, syndecans potentiate the action of agouti-related prot ein and agouti signaling protein, endogenous inhibitors of alpha MSH. In wi ld-type mice, syndecan-3, the predominantly neural syndecan, is expressed i n hypothalamic regions that control energy balance. Food deprivation increa ses hypothalamic syndecan-3 levels several-fold. Syndecan-3 null mice, othe rwise apparently normal, respond to food deprivation with markedly reduced reflex hyperphagia. We propose that oscillation of hypothalamic syndecan-3 levels physiologically modulates feeding behavior.