NEUROPEPTIDE-Y, THE HYPOTHALAMUS AND THE REGULATION OF ENERGY HOMEOSTASIS

Neuropeptide Y (NPY) neurones in the arcuate nucleus of the rodent hyp othalamus may play a key role in responding to reductions in body ener gy stores with appropriate changes in energy homeostasis, namely an in crease in food-seeking behaviour and hyperphagia, together with a redu ction in heat production by brown adipose tissue. These adaptive respo nses are mimicked by the injection of NPY into the main sites of proje ction of the NPY neurones, and animals that are threatened by energy d eficits (e.g. through starvation or insulin-deficient diabetes) show i ncreased activity of these neurones. Genetically obese rodents also sh ow hyperactivity of the NPY neurones, which is inappropriate to their energy needs and may contribute to their hyperphagia, reduced energy e xpenditure and excessive weight gain. The NPY neurones may be inhibite d by insulin and leptin, which may both serve as signals of peripheral fat mass. Ultimately, characterization of the specific 'feeding' rece ptors which mediate NPY's central effects on energy homeostasis may pr ovide opportunities for designing drugs to manipulate appetite and ene rgy balance in man, notably obesity and the cachexia commonly associat ed with malignancy and chronic infection.