PACAP neurons in the hypothalamic ventromedial nucleus are targets of central leptin signaling.

The adipose-derived hormone, leptin, was discovered over 10 years ago, but only now are we unmasking its downstream pathways which lead to reduced energy intake (feeding) and increased energy expenditure (thermogenesis). Recent transgenic models have challenged the long-standing supposition that the hypothalamic arcuate nucleus (Arc) is omnipotent in the central response to leptin, and research focus is beginning to shift to examine roles of extra-arcuate sites. Dhillon et al.

Appetite-modifying actions of pro-neuromedin U-derived peptides.

Neuromedin U (NMU) is known to have potent actions on appetite and energy expenditure. Deletion of the NMU gene in mice leads to an obese phenotype, characterized by hyperphagia and decreased energy expenditure. Conversely, transgenic mice that overexpress proNMU exhibit reduced body weight and fat storage.

Evaluation of neuromedin U actions in energy homeostasis and pituitary function.

The brain-gut peptide neuromedin U (NMU) has been identified recently as a physiological regulator of food intake. To further investigate the central role of NMU in energy homeostasis, we examined the distribution of NMU transcript and the effect of intracerebroventricular administration on several physiological parameters and on the pattern of c-Fos activation. Here we report that intracerebroventricular administration of NMU to 24-h fasted rats resulted in a decrease in subsequent food intake and body weight gain.

Photoperiodic regulation of leptin resistance in the seasonally breeding Siberian hamster (Phodopus sungorus).

Seasonal Siberian hamsters lose fat reserves, decrease body weight and leptin concentrations, and suppress reproduction on short-day photoperiod (SD). Chronic leptin infusion at physiological doses caused body weight and fat loss in SD animals but was ineffective in long-day (LD) hamsters. Using ovariectomized estrogen-treated females, we tested the hypothesis that responsiveness to leptin is regulated by photoperiod.