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Late-onset leanness in mice with targeted ablation of melanin concentrating hormone neurons.

Abstract
The observation that loss of orexin (hypocretin) neurons causes human narcolepsy raises the possibility that other acquired disorders might also result from loss of hypothalamic neurons. To test this possibility for body weight, mice with selective loss of melanin concentrating hormone (MCH) neurons were generated. MCH was chosen to test because induced mutations of the MCH gene in mice cause hypophagia and leanness. Mice with ablation of MCH neurons were generated using toxin (ataxin-3)-mediated ablation strategy. The mice appeared normal but, after 7 weeks, developed reduced body weight, body length, fat mass, lean mass, and leptin levels. Leanness was characterized by hypophagia and increased energy expenditure. To study the role of MCH neurons on obesity secondary to leptin deficiency, we generated mice deficient in both ob gene product (leptin) and MCH neurons. Absence of MCH neurons in ob/ob mice improved obesity, diabetes, and hepatic steatosis, suggesting that MCH neurons are important mediators of the response to leptin deficiency. These data show that loss of MCH neurons can lead to an acquired leanness. This has implications for the pathogenesis of acquired changes of body weight and might be considered in clinical settings characterized by substantial weight changes later in life.
AuthorsTamar Alon, Jeffrey M Friedman
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci) Vol. 26 Issue 2 Pg. 389-97 (Jan 11 2006) ISSN: 1529-2401 [Electronic] United States
PMID16407534 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Ataxin-3
  • Atxn3 protein, mouse
  • Blood Glucose
  • Hypothalamic Hormones
  • Insulin
  • Leptin
  • Melanins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Nuclear Proteins
  • Pituitary Hormones
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Transcription Factors
  • melanin-concentrating hormone
  • ATXN3 protein, human
Topics
  • Adipose Tissue (pathology)
  • Animals
  • Ataxin-3
  • Blood Glucose (analysis)
  • Cell Death
  • Crosses, Genetic
  • Diabetes Mellitus, Experimental (physiopathology)
  • Energy Intake
  • Energy Metabolism
  • Fasting (blood)
  • Fatty Liver (physiopathology)
  • Female
  • Gene Expression
  • Hypothalamic Hormones (analysis, physiology)
  • Hypothalamus (pathology, physiopathology)
  • Insulin (blood)
  • Leptin (deficiency, genetics, therapeutic use)
  • Machado-Joseph Disease (genetics)
  • Male
  • Melanins (analysis, physiology)
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Nerve Tissue Proteins (genetics, physiology)
  • Neurons (physiology)
  • Neuropeptides (metabolism)
  • Nuclear Proteins
  • Obesity (genetics, physiopathology)
  • Pituitary Hormones (analysis, physiology)
  • Recombinant Fusion Proteins (physiology)
  • Repressor Proteins
  • Thinness (etiology)
  • Transcription Factors
  • Weight Loss

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