Insulin resistance of hypothalamic arcuate neurons in neonatally overfed rats.

Rats exposed to early postnatal overfeeding by rearing in small litters become hyperphagic, hyperleptinemic, and hyperinsulinemic throughout later life. Medial arcuate neurons are involved in body weight regulation. They were tested in brain slices of control and small-litter rats concerning differences in responses to insulin. Insulin induced suppression of firing in controls, whereas in small-litter rats inhibition was significantly reduced and activation increased. This could be observed in juvenile as well as adult rats. A gamma-aminobutyric acid type A receptor antagonist did not change the responses. Thus, negative feedback to the satiety signal insulin on medial arcuate neurons is reduced in neonatally overfed small-litter rats. This can be regarded as insulin resistance, which is induced during early development and persists in later life.