Introduction

Our knowledge of the potential genetic link between fat metabolism and the reproductive axis dates back to the 1950s when the obese (ob/ob) mouse strain was first described. These mice were not only distinctly hyperphagic and rapidly developed obesity associated with hyperglycaemia and insulin resistance, but they were also infertile.¹ It was not until 1994 when the leptin (ob) gene was postionally cloned and a mutation was identified in the coding sequence of murine leptin in ob/ob mice that the cause of their obesity was recognised.² As predicted from the phenotype of ob/ob mice, leptin, which is principally expressed in adipocytes, had potent actions to suppress appetite and stimulate energy expenditure. It rapidly became clear that leptin could also influence the reproductive system. The sterility of male and female ob/ob mice could be reversed when recombinant leptin was administered.^3 4

In humans, initial studies focused on the possible . . . [Full text of this article]