Hyperphagia induced by hypoglycemia in rats is independent of leptin and hypothalamic neuropeptide Y (NPY)

Hypoglycemia causes hyperphagia and weight gain, through unknown peripheral and central signals. We investigated the effect of hypoglycemia on NPY and leptin expression and the ability of leptin to inhibit hypoglycemia-induce d hyperphagia. Acute hypoglycemia (60 U/kg SC insulin; n = 8) increased foo d intake (p < 0.01) compared with controls (n = 8). Insulin- and leptin-tre ated rats (300 mu g/kg IP leptin; n = 8) had reduced hyperphagia (p < 0.05 vs, controls; p < 0.05 vs. insulin alone) and a 15% fall in NPY mRNA levels compared with controls (p < 0.01). Chronic hypoglycemia, (20-60 U/kg/day i nsulin; n = 8) increased food intake compared with vehicle-treated controls (p < 0.01). Leptin and insulin administration (300 mu g/kg/day IP leptin; n = 8) reduced hyperphagia (p < 0.01 vs. controls, p < 0.05 vs. insulin alo ne), and NPY mRNA fell by 18% vs. controls (p < 0.01). We conclude that hyp oglycemia-induced hyperphagia is not mediated by either a fall in leptin or an increase in hypothalamic NPY mRNA. Leptin can inhibit feeding in hyperp hagic hypoglycemic rats, and this may partly be attributable to its inhibit ion of the NPY neurons. (C) 1998 Elsevier Science Inc.