The hypothalamic neurocircuitry which regulates energy homeostasis in adult rats is not fully developed until the third postnatal week. In particular, fibers from the hypothalamic arcuate nucleus, including both neuropeptide Y (NPY) and -melanocyte-stimulating hormone (-MSH) fibers, do not begin to innervate downstream hypothalamic targets until the second postnatal week. However, -MSH fibers from the brainstem and melanocortin receptors are present in the hypothalamus at birth. The present study investigated the melanocortin system in the early postnatal period by examining effects of the melanocortin receptor agonist MTII on body weight, energy expenditure and hypothalamic NPY expression.

Rat pups were injected ip with MTII (3 mg/kg bw) or saline on postnatal day (P)5-6, P10-11 or P15-16, at 1700h and 0900h, then sacrificed at 1300h. Stomach weight and brown adipose tissue (BAT) uncoupling-protein 1 (UCP1) mRNA were determined. In addition we assessed central c-Fos activation 90 min after MTII administration and hypothalamic NPY mRNA following twice daily MTII administration from P5-10 or P10-15.

MTII induced hypothalamic c-Fos activation as well as attenuating body weight gain in rat pups. Stomach weight was significantly decreased and UCP1 mRNA was increased at all ages, indicating decreased food intake and increased energy expenditure, respectively. However, MTII had no effect on NPY mRNA levels in any hypothalamic region. These findings demonstrate that MTII can inhibit food intake and stimulate energy expenditure prior to the full development of hypothalamic feeding neurocircuitry. These effects do not appear to be mediated by changes in NPY expression.