Effects of acute and chronic administration of the melanocortin agonist MTII in mice with diet-induced obesity. Diabetes 51:1337–1345

High-fat diet–induced obesity (DIO) in rodents is asso-ciated with hyperleptinemia and resistance to leptin, but the response to agents acting downstream of leptin receptors remains unknown. We assessed the response of mice with DIO to treatment with MTII, an -melano-cyte-stimulating hormone analog. MTII delivered four times daily by intraperitoneal injection to C57BL/6J mice produced a dose-responsive effect on food intake, body weight, leptin, corticosterone, insulin, and free fatty acids. In DIO mice, administration of MTII 100 g q.i.d. i.p. markedly suppressed feeding during the first 4 days of treatment, with food intake returning to control levels at day 5. Progressive weight loss also occurred over the first 4 days, after which weight plateaued at a level below control. After 8 days of treatment, MTII