Obesity is a serious health problem in the Western societies, therefor
e its treatment has become the subject of intense interest in the scie
ntific community. A significant number of recent publications enlist d
ifferent central and peripheral factors which play important roles in
the regulation of food intake, body weight and energy expenditure. Neu
ropeptide Y, a 36 amino acid peptide, which is quite abundant in the b
rain, seems to be one of the more important players in these regulatio
ns. Recently five NPY receptors have been cloned and pharmacological e
vidence strongly supports the existence of a sixth receptor. There are
many contradictory findings regarding which NPY receptor mediates the
effect of NPY on food intake. This article will review the effects of
NPY on the regulation of food intake and energy expenditure and will
discuss the pharmacological and molecular evidence as to which NPY rec
eptor(s) mediate this effect. The review will also summarize the progr
ess which has been made in the design of novel NPY-ergic ligands, espe
cially NPY receptor antagonists, for potential use in the treatment of
obesity.