Increased beta-endorphin and dynorphin concentrations in discrete hypothalamic regions of genetically obese (ob/ob)...

Disturbances in hypothalamic beta-endorphin and dynorphin levels were investigated in non-fasted genetically obese (ob/ob) and homozygous lean mice at 14-15 weeks of age. Eight brain regions were microdissected from fresh, unfixed brain slices, and opioid peptide concentrations were determined in tissue micropunches by radioimmunoassay. A two-fold and five-fold increase in beta-endorphin levels in ob/ob versus lean mice were found in the ventromedial and dorsomedial hypothalamic nuclei respectively. Dynorphin levels were comparable between ob/ob and lean mice in the anterior, lateral, ventromedial and paraventricular hypothalamic areas, but a 5-fold increase in dynorphin concentrations was detected in the dorsomedial hypothalamic nucleus of the ob/ob mouse. These results demonstrate that increased concentrations of beta-endorphin and dynorphin occur in discrete hypothalamic nuclei, which are known to influence food intake and glucose homeostasis. This could signify an important central defect contributing to hyperphagia and glucoregulatory dysfunction in obese mice.