This Article Full Text Full Text (PDF) All Versions of this Article: 149/3/971    most recent Author Manuscript (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ladenheim, E. E. Articles by Moran, T. H. Search for Related Content PubMed PubMed Citation Articles by Ladenheim, E. E. Articles by Moran, T. H.

Factors Contributing to Obesity in Bombesin Receptor Subtype-3-Deficient Mice

Department of Psychiatry and Behavioral Sciences (E.E.L., N.L.H., R.R.B., S.B., T.H.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; and National Institute of Neurological Disorders and Stroke (L.L.H., J.F.B.), National Institutes of Health, Bethesda, Maryland 20892

Address all correspondence and requests for reprints to: Ellen E. Ladenheim, Ph.D., Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, Ross 618, 720 Rutland Avenue, Baltimore, Maryland 21205. E-mail: laden{at}jhmi.edu.

Mice with a targeted disruption of bombesin receptor subtype-3 (BRS-3 KO) develop hyperphagia, obesity, hypertension, and impaired glucose metabolism. However, the factors contributing to their phenotype have not been clearly established. To determine whether their obesity is a result of increased food intake or a defect in energy regulation, we matched the caloric intake of BRS-3 KO mice to wild-type (WT) ad libitum (ad lib)-fed controls over 21 wk. Although BRS-3 KO ad lib-fed mice were 29% heavier, the body weights of BRS-3 KO pair-fed mice did not differ from WT ad lib-fed mice. Pair-feeding BRS-3 KO mice normalized plasma insulin but failed to completely reverse increased adiposity and leptin levels. Hyperphagia in ad lib-fed KO mice was due to an increase in meal size without a compensatory decrease in meal frequency resulting in an increase in total daily food intake. An examination of neuropeptide Y, proopiomelanocortin, and agouti-related peptide gene expression in the arcuate nucleus revealed that BRS-3 KO mice have some deficits in their response to energy regulatory signals. An evaluation of the satiety effects of cholecystokinin, bombesin, and gastrin-releasing peptide found no differences in feeding suppression by these peptides. We conclude that hyperphagia is a major factor leading to increased body weight and hyperinsulinemia in BRS-3 KO mice. However, our finding that pair-feeding did not completely normalize fat distribution and plasma leptin levels suggests there is also a metabolic dysregulation that may contribute to, or sustain, their obese phenotype.