Hypothalamic
obesity (HO) is a major and unsolved problem in patients with medial hypothalamic lesions and is associated with
hyperinsulinemia and hyperleptinemia. The purpose of this study was to create a rodent model that mimics metabolic changes in HO for use in therapeutic testing. Female Sprague-Dawley rats were used to test the individual and combined effects of two types of medial hypothalamic lesions: arcuate nucleus (
ARC) lesions by injection of
monosodium glutamate at neonatal age, and ventromedial nucleus (VMN) lesions by passing an anodal current through an
electrode placed in the VMN at age 80 days. Adiposity in
ARC-lesioned animals was associated with decreased food intake and
stunted growth, while VMN lesions were associated with
hyperphagia but not reduced growth. The greatest
weight gain (weight at age 200 days 712 +/- 65 vs. 451 +/- 19 g in controls),
hyperphagia (food intake 10 days following surgery 33 +/- 0.8 vs. 18.5 +/- 0.7 g/day in
sham-treated rats),
hyperinsulinemia and hyperleptinemia occurred in rats that received both
ARC and VMN lesions. Thus, the combined medial hypothalamic lesions result in an
obesity phenotype similar to that of patients that suffer from HO and are consequently more suitable for testing potential
therapeutics for this disorder than lesions of single hypothalamic nuclei.