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Blunted fasting-induced hypothalamic activation and refeeding hyperphagia in late-onset obesity.

Abstract
Hormonal and metabolic factors signal the status of energy balance to hypothalamic nuclei. Obesity is characterized by neuronal, metabolic and hormonal alterations. We therefore hypothesized that hypothalamic responses to challenges of energy balance may differ between lean and obese animals. To test this, we compared c-Fos expression in the hypothalamic arcuate (ARC) and paraventricular nuclei (PVN) and the lateral hypothalamic area (LHA) of mice (1-year-old) with late-onset obesity (LOO) and of lean controls under different feeding conditions. Fourteen hours of fasting induced high c-Fos expression in neuropeptide-Y-positive ARC neurons, in the PVN and in the rostral LHA in lean but not in LOO mice. c-Fos expression in melanin-concentrating hormone (MCH) and orexin-containing neurons in the caudal LHA was not affected by fasting. LOO mice showed fasting hyperinsulinemia, hyperleptinemia, elevated fasting blood glucose and an attenuated hyperphagic response during refeeding. Moreover, the anorectic response to leptin and hypoglycemic response to insulin were reduced in LOO mice. We conclude that adiposity blunts the neuronal responses to metabolic challenges in hypothalamic centers which control feeding behavior and energy balance. Elevated blood glucose may be one factor that suppresses hypothalamic responsiveness in obese mice. A similar impact of hyperinsulinemia and hyperleptinemia in LOO mice is also likely although under the current experimental conditions responsiveness to some effects of these hormones appeared to be reduced.
AuthorsCsilla Becskei, Thomas A Lutz, Thomas Riediger
JournalNeuroendocrinology (Neuroendocrinology) Vol. 90 Issue 4 Pg. 371-82 ( 2009) ISSN: 1423-0194 [Electronic] Switzerland
PMID19844081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright 2009 S. Karger AG, Basel.
Chemical References
  • Blood Glucose
  • Intracellular Signaling Peptides and Proteins
  • Leptin
  • Melanins
  • Neuropeptide Y
  • Neuropeptides
  • Orexins
  • Proto-Oncogene Proteins c-fos
  • Green Fluorescent Proteins
Topics
  • Age of Onset
  • Animals
  • Arcuate Nucleus of Hypothalamus (physiopathology)
  • Blood Glucose (physiology)
  • Fasting (physiology)
  • Green Fluorescent Proteins (genetics)
  • Hyperinsulinism (physiopathology)
  • Hyperphagia (physiopathology)
  • Hypothalamic Area, Lateral (physiopathology)
  • Intracellular Signaling Peptides and Proteins (metabolism)
  • Leptin (blood)
  • Male
  • Melanins (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons (physiology)
  • Neuropeptide Y (metabolism)
  • Neuropeptides (metabolism)
  • Obesity (physiopathology)
  • Orexins
  • Paraventricular Hypothalamic Nucleus (physiopathology)
  • Proto-Oncogene Proteins c-fos (metabolism)

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