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

Colleen M. Novak, Minzhi Zhang, James A. Levine

Research output: Contribution to journalArticle

20 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)57-68
Number of pages12
JournalBrain Research
Volume1169
Issue number1
DOIs
StatePublished - Sep 12 2007
Externally publishedYes

Fingerprint

Paraventricular Hypothalamic Nucleus
Obesity
Energy Metabolism
Diet
High Fat Diet
Thermogenesis
Microinjections
Neuropeptides
neuromedin U
Appetite
Energy Intake
Fats
Hormones
Peptides
Brain

Keywords

  • Diet-induced obese (DIO) rats
  • Energy expenditure
  • NEAT
  • Non-exercise activity thermogenesis
  • Obesity
  • Physical activity

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity. / Novak, Colleen M.; Zhang, Minzhi; Levine, James A.

In: Brain Research, Vol. 1169, No. 1, 12.09.2007, p. 57-68.

Research output: Contribution to journalArticle

Novak, Colleen M. ; Zhang, Minzhi ; Levine, James A. / Sensitivity of the hypothalamic paraventricular nucleus to the locomotor-activating effects of neuromedin U in obesity. In: Brain Research. 2007 ; Vol. 1169, No. 1. pp. 57-68.
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