Effects of hypothalamic neurodegeneration on energy balance
- PMID: 16296893
- PMCID: PMC1287504
- DOI: 10.1371/journal.pbio.0030415
Effects of hypothalamic neurodegeneration on energy balance
Abstract
Normal aging in humans and rodents is accompanied by a progressive increase in adiposity. To investigate the role of hypothalamic neuronal circuits in this process, we used a Cre-lox strategy to create mice with specific and progressive degeneration of hypothalamic neurons that express agouti-related protein (Agrp) or proopiomelanocortin (Pomc), neuropeptides that promote positive or negative energy balance, respectively, through their opposing effects on melanocortin receptor signaling. In previous studies, Pomc mutant mice became obese, but Agrp mutant mice were surprisingly normal, suggesting potential compensation by neuronal circuits or genetic redundancy. Here we find that Pomc-ablation mice develop obesity similar to that described for Pomc knockout mice, but also exhibit defects in compensatory hyperphagia similar to what occurs during normal aging. Agrp-ablation female mice exhibit reduced adiposity with normal compensatory hyperphagia, while animals ablated for both Pomc and Agrp neurons exhibit an additive interaction phenotype. These findings provide new insight into the roles of hypothalamic neurons in energy balance regulation, and provide a model for understanding defects in human energy balance associated with neurodegeneration and aging.
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References
-
- Elia M. Obesity in the elderly. Obes Res. 2001;9:244S–248S. - PubMed
-
- Roberts SB, Dallal GE. Effects of age on energy balance. Am J Clin Nutr. 1998;68:975S–979S. - PubMed
-
- Roberts SB. Energy regulation and aging: Recent findings and their implications. Nutr Rev. 2000;58:91–97. - PubMed
-
- Roberts SB. A review of age-related changes in energy regulation and suggested mechanisms. Mech Ageing Dev. 2000;116:157–167. - PubMed
-
- Mizuno T, Shu IW, Makimura H, Mobbs C. Obesity over the life course. Sci Aging Knowledge Environ. 2004 re4. - PubMed
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