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Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity

Item Type:Article
Title:Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity
Creators Name:Rios, M. and Fan, G. and Fekete, C. and Kelly, J. and Bates, B. and Kuehn, R. and Lechan, R.M. and Jaenisch, R.
Abstract:Brain-derived neurotrophic factor has been associated previously with the regulation of food intake. To help elucidate the role of this neurotrophin in weight regulation, we have generated conditional mutants in which brain-derived neurotrophic factor has been eliminated from the brain after birth through the use of the cre-loxP recombination system. Brain-derived neurotrophic factor conditional mutants were hyperactive after exposure to stressors and had higher levels of anxiety when evaluated in the light/dark exploration test. They also had mature onset obesity characterized by a dramatic 80-150% increase in body weight, increased linear growth, and elevated serum levels of leptin, insulin, glucose, and cholesterol. In addition, the mutants had an abnormal starvation response and elevated basal levels of POMC, an anorexigenic factor and the precursor for alpha-MSH. Our results demonstrate that brain derived neurotrophic factor has an essential maintenance function in the regulation of anxiety-related behavior and in food intake through central mediators in both the basal and fasted state.
Keywords:Anxiety, Body Weight, Brain, Brain-Derived Neurotrophic Factor, Fasting, Fluoxetine, Gene Deletion, Gene Expression, Hyperglycemia, Hyperinsulinism, Hyperkinesis, Hypothalamus, Integrases, Leptin, Messenger RNA, Neuropeptide Y, Obesity, Pro-Opiomelanocortin, Serotonin, Serotonin Uptake Inhibitors, Transfection, Viral Proteins, Animals, Mice
Source:Molecular Endocrinology
Publisher:Endocrine Society
Page Range:1748-1757
Date:October 2001
Official Publication:https://doi.org/10.1210/mend.15.10.0706
PubMed:View item in PubMed

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