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Cited by 35Regulation of Appetite and ObesityHypothalamic control of reproductive hormonesPituitary Gland Disorders and Treatments

A Novel Rodent Model That Mimics the Metabolic Sequelae of Obese Craniopharyngioma Patients

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Roth, Christian L, Blevins, James E, Ralston, Melissa, Elfers, Clinton, Ogimoto, Kayoko, Kaiyala, Karl J, Morton, Gregory J·2011·Pediatric Research
DOI 10.1203/pdr.0b013e3182083b67PMC PMC3673774
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Abstract

Patients with craniopharyngioma (CP), a tumor located in the pituitary and/or hypothalamus, are susceptible to developing obesity and many metabolic complications. The study aim was to create a rodent model that mimics the complex neuroanatomical and metabolic disturbances commonly seen in obese CP patients. We compared the metabolic phenotype of animals with three distinct types of hypothalamic lesions: 1) destruction of the arcuate nucleus (ARC) induced by monosodium glutamate (MSG), 2) electrolytic lesion of the adjacent ventromedial nucleus (VMN) alone, 3) both the VMN and dorsomedial nucleus (DMN), or a 4) combined medial hypothalamic lesion (CMHL) affecting the VMN, DMN, and the ARC. Only the CMHL model exhibited all key features observed in patients with hypothalamic obesity induced by CP. These features included excessive weight gain due to increased adiposity, increased food intake, and pronounced hyperinsulinemia and hyperleptinemia. Similar to characteristics of patients with CP, CMHL animals exhibited reduced plasma levels of alpha-melanocyte stimulating hormone and reduced ambulatory activity compared with weight-matched controls. Therefore, the CMHL model best mimics the complex metabolic abnormalities observed in obese CP patients compared with lesions to other hypothalamic areas and provides a foundation for future pharmacological approaches to treat obesity in children with hypothalamic damage.

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  • The hypothalamus, particularly the ventromedial and dorsomedial nuclei, integrates signals from the autonomic nervous system that govern heart rate, blood pressure, respiratory rate, body temperature, and digestion.

    “First, the hypothalamus, in particular the ventromedial and dorsomedial hypothalamic nuclei, integrates signals from the autonomic nervous system that govern physiologic processes including heart rate, blood pressure, respiratory rate, body temperature, and digestion (53-56).”

    From Approach to the patient with acquired hypothalamic syndrome (2026) · cites this paper as [55]

    The Discussion (page unavailable) says hypothalamic pathways regulate autonomic outflow, and the Results (page unavailable) show that VMN and VMN/DMN lesions affect food intake and body weight. The paper does not say these nuclei integrate signals from the autonomic nervous system or link them to heart rate, blood pressure, respiratory rate, body temperature, and digestion. (LLM, conf=0.84)

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Cited by

Sorted by citations

Authors
Roth, C. L., Blevins, J. E., Ralston, M., Elfers, C., Ogimoto, K., Kaiyala, K. J., & Morton, G. J.
Affiliations
  • University of Washington (US)
  • VA Puget Sound Health Care System (US)
Corresponding author
Roth, Christian L
ORCID
Venue
Pediatric Research
Publisher
Springer Science and Business Media LLC
Published
2011-03
Volume
69
Issue
3
Pages
230-236
ISSN
  • 0031-3998 (ISSN-L)
  • 1530-0447
DOI
10.1203/pdr.0b013e3182083b67
PMC
PMC3673774
OpenAlex
W1963695250
Cited by
35
References
2
Citations by year
2026: 2 · 2024: 1 · 2022: 11 · 2021: 3 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 3
FWCI
1.16
Type
journal article
Language
en
Open access
Locations
  • Pediatric Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • University of Washington (DK‐035816)
  • Nutrition Obesity Research Center, University of North Carolina (DK035816)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089056, DK 035816, P30DK035816)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
Keywords
craniopharyngioma, hypothalamic obesity, rodent models, hypothalamic lesions, arcuate nucleus, ventromedial hypothalamus, dorsomedial nucleus, hyperinsulinemia, hyperleptinemia, alpha-melanocyte-stimulating hormone, dietary intake, ambulatory activity, childhood obesity
MeSH terms
Animals, Arcuate Nucleus of Hypothalamus, Body Weight, Child, Craniopharyngioma, Disease Models, Animal, Dorsomedial Hypothalamic Nucleus, Eating, Energy Metabolism, Female, Homeostasis, Humans, Hypothalamic Neoplasms, Hypothalamus, Male, Obesity, Pituitary Neoplasms, Pregnancy, Sodium Glutamate, Ventromedial Hypothalamic Nucleus, Rats, Sprague-Dawley, Rats

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