Melanin-concentrating hormone regulates leptin synthesis and secretion in rat adipocytes

Obesity is a common problem in Western society and is associated with signi ficant morbidity and mortality. Energy homeostasis is regulated by a comple x system involving both peripheral signals such as leptin and a number of o rexigenic and anorectic neuropeptides. Obesity can result from dysregulatio n of the peripheral and/or central signals. Melanin-concentrating hormone ( MCH) is a hypothalamic peptide that is important in the regulation of feedi ng behavior, primarily via uncharacterized signaling pathways in the centra l nervous system. Leptin, expressed in adipose tissue, mediates some of its actions through several hypothalamic neuropeptides, notably agouti-related peptide, proopiomelanocortin, and neuropeptide Y. Expression of leptin is regulated by dietary status, insulin, and glucocorticoids. Furthermore, cer tain neuropeptides may act on adipocytes. However, the potential effect of MCH has not been investigated. We report that MCH stimulates leptin mRNA ex pression and leptin secretion. MCH stimulated a 2-fold increase in leptin s ecretion by isolated rat adipocytes after 4 h of treatment. This increase i n secreted leptin was preceded by a rapid and transient increase in ob mRNA levels; MCH stimulated a 2.5-fold increase in ob mRNA within 1 h of treatm ent, followed by a decline to basal levels within 4 h. In addition, we demo nstrate that the MCH receptor SLC-1 is expressed in adipocytes, suggesting that fat cells may be targets of MCH or an MCH-like peptide under physiolog ical conditions. Finally, using a radioimmunoassay, MCH/MCH-like peptide wa s detected in rat plasma. This study establishes a novel in vitro mammalian system for examining MCH signaling pathways.