Effects of hypothalamic neurodegeneration on energy balance.

Allison Wanting Xu, Christopher B. Kaelin, Gregory J. Morton, Kayoko Ogimoto, Kimber Stanhope, James Graham, Denis G. Baskin, Peter Havel, Michael W. Schwartz, Gregory S. Barsh

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalPLoS Biology
Volume3
Issue number12
StatePublished - Dec 2005
Externally publishedYes

Fingerprint

Pro-Opiomelanocortin
Agouti-Related Protein
pro-opiomelanocortin
Energy balance
energy balance
Agouti
mice
Neurons
Hyperphagia
Aging of materials
Adiposity
overeating
Ablation
neurons
adiposity
Melanocortin Receptors
proteins
Obese Mice
Nerve Degeneration
Defects

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Xu, A. W., Kaelin, C. B., Morton, G. J., Ogimoto, K., Stanhope, K., Graham, J., ... Barsh, G. S. (2005). Effects of hypothalamic neurodegeneration on energy balance. PLoS Biology, 3(12).

Effects of hypothalamic neurodegeneration on energy balance. / Xu, Allison Wanting; Kaelin, Christopher B.; Morton, Gregory J.; Ogimoto, Kayoko; Stanhope, Kimber; Graham, James; Baskin, Denis G.; Havel, Peter; Schwartz, Michael W.; Barsh, Gregory S.

In: PLoS Biology, Vol. 3, No. 12, 12.2005.

Research output: Contribution to journalArticle

Xu, AW, Kaelin, CB, Morton, GJ, Ogimoto, K, Stanhope, K, Graham, J, Baskin, DG, Havel, P, Schwartz, MW & Barsh, GS 2005, 'Effects of hypothalamic neurodegeneration on energy balance.', PLoS Biology, vol. 3, no. 12.
Xu AW, Kaelin CB, Morton GJ, Ogimoto K, Stanhope K, Graham J et al. Effects of hypothalamic neurodegeneration on energy balance. PLoS Biology. 2005 Dec;3(12).
Xu, Allison Wanting ; Kaelin, Christopher B. ; Morton, Gregory J. ; Ogimoto, Kayoko ; Stanhope, Kimber ; Graham, James ; Baskin, Denis G. ; Havel, Peter ; Schwartz, Michael W. ; Barsh, Gregory S. / Effects of hypothalamic neurodegeneration on energy balance. In: PLoS Biology. 2005 ; Vol. 3, No. 12.
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