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Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity.

Abstract
Obesity is associated with a decrease in energy expenditure relative to energy intake. The decrease in physical activity associated with obesity in several species, including humans, contributes to decreased energy expenditure. Several hormones and neuropeptides that affect appetite also modulate physical activity, including neuromedin U (NMU), a peptide found in the gut and brain. We have demonstrated that NMU microinjected into the hypothalamic paraventricular nucleus (PVN) in rats increases the energy expenditure associated with physical activity, called non-exercise activity thermogenesis (NEAT). Here we examined whether obesity in rats is related to decreased sensitivity of the PVN to the locomotor-activating effect of NMU. Diet-induced obese (DIO) rats and lean, diet-resistant (DR) rats were given PVN microinjections of increasing doses of NMU both before and after 1 month on a high-fat diet. We found that NMU increases physical activity, energy expenditure, and NEAT in a dose-dependent manner in both DR and DIO rats, both before and after 1 month on the high-fat diet. Before high-fat feeding, the obesity-prone and lean rats showed similar levels of physical activity after intra-PVN microinjections of NMU. After 1 month of the high-fat diet, however, the obesity-resistant rats showed significantly more NMU-induced physical activity compared to the obese DIO rats. Taken together with previous studies, these results suggest that obesity may represent a state associated with decreased central sensitivity to neuropeptides such as NMU that increase physical activity and therefore energy expenditure.
AuthorsColleen M Novak, Minzhi Zhang, James A Levine
JournalBrain research (Brain Res) Vol. 1169 Pg. 57-68 (Sep 12 2007) ISSN: 0006-8993 [Print] Netherlands
PMID17706946 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Dietary Fats
  • Neuropeptides
  • neuromedin U
Topics
  • Animals
  • Body Weight (drug effects, physiology)
  • Dietary Fats (pharmacology)
  • Dose-Response Relationship, Drug
  • Drug Resistance (genetics)
  • Energy Metabolism (drug effects, genetics)
  • Exploratory Behavior (drug effects, physiology)
  • Food, Formulated
  • Genetic Predisposition to Disease (genetics)
  • Male
  • Motor Activity (drug effects, physiology)
  • Neuropeptides (metabolism, pharmacology)
  • Obesity (genetics, metabolism, physiopathology)
  • Paraventricular Hypothalamic Nucleus (drug effects, metabolism)
  • Physical Conditioning, Animal
  • Rats
  • Rats, Sprague-Dawley
  • Thermogenesis (drug effects, physiology)

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