Adrenalectomy reverses obese phenotype and restores hypothalamic melanocortin tone in leptin-deficient ob/ob mice

Hideo Makimura, Tooru M. Mizuno, James Roberts, Jeff Silverstein, Joe Beasley, Charles V. Mobbs

Research output: Contribution to journalArticlepeer-review

88 Scopus citations


In genetically obese leptin-deficient ob/oh mice, adrenalectomy reverses or attenuates the obese phenotype. Relative to lean controls, ob/ob mice also exhibit decreased hypothalamic proopiomelanocortin (POMC) mRNA and increased hypothalamic agouti-related peptide (AGRP) mRNA and neuropeptide Y (NPY) mRNA. It has been hypothesized that this profile of hypothalamic gene expression contributes to the obese phenotype caused by leptin deficiency. To assess if reversal of obese phenotype by adrenalectomy entails normalization of hypothalamic gene expression, male wild-type and ob/ob mice were adrenalectomized (with saline supplementation) or sham adrenalectomized at 2 months of age. Mice were sacrificed 2 weeks after adrenalectomy, during which time food intake and body weight were monitored daily. After sacrifice, hypothalamic gene expression was assessed by Northern blot analysis as well as in situ hybridization. In wild-type mice, adrenalectomy significantly decreased AGRP mRNA but did not significantly influence POMC or NPY mRNA. In ob/ob mice, adrenalectomy reduced the levels of plasma glucose, serum insulin and corticosterone, and food intake toward or below wild-type levels, and it restored hypothalamic POMC and AGRP mRNA but not NPY mRNA to wild-type levels. These studies suggest that adrenalectomy reverses or attenuates the obese phenotype in ob/ob mice, in part by restoring hypothalamic melanocortin tone toward wild-type levels. These studies also demonstrate that factors other than leptin may play a major role in regulating hypothalamic melanocortin function.

Original languageEnglish
Pages (from-to)1917-1923
Number of pages7
Issue number11
StatePublished - 2000


Dive into the research topics of 'Adrenalectomy reverses obese phenotype and restores hypothalamic melanocortin tone in leptin-deficient ob/ob mice'. Together they form a unique fingerprint.

Cite this