A role for agouti-related protein in appetite regulation in a species with continuous nutrient delivery

Christine G. Wagner, Chris D. McMahon, Daniel Marks, Joseph A. Daniel, Barbara Steele, James L. Sartin

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Knowledge of specific neurotransmitters as well as the pathways and mechanisms regulating appetite in ruminants that continually graze, such as sheep, is incomplete. Although fundamentally agouti-related protein (AGRP) has a similar function across species to increase food intake, the regulation of AGRP may vary across grazing and intermittent feeders. To investigate the role of orexigenic peptides in the regulation of feed intake, we first extracted messenger RNA from sheep that were fasted for 3 days, which was then used for PCR followed by cloning and sequencing to demonstrate the presence of hypothalamic AGRP expression. Ovine AGRP was closely related to the bovine, but contained sequence differences with human and mouse AGRP. Analysis of genomic DNA also revealed a similar gene structure to other published species. Secondly, using dual-labeled immunohistochemistry, we determined that there was both increased AGRP immunoreactivity and increased abundance of c-Fos immunoreactivity in AGRP neurons in the arcuate nucleus of fasted sheep. Because AGRP neurons are activated by fasting, we hypothesized that AGRP would stimulate feeding in this ruminant species. Sheep fed ad libitum were injected intracerebroventricularly with concentrations of AGRP at 0.2 and 2.0 nmol/kg. AGRP at 2.0 nmol/kg significantly increased food intake at 4, 6 and 12 h (p <0.05). A 4th study was done to investigate the interactions of AGRP and neuropeptide Y (NPY) on food intake over a 24-hour period. Intracerebroventricular injections of either AGRP or NPY significantly increased cumulative food intake over saline controls. When AGRP and NPY were injected in combination, food intake was increased over saline controls; however, AGRP did not potentiate the effects of NPY. These results demonstrate that AGRP stimulates food intake in sheep and highlights the important differences between this species and rodent models.

Original languageEnglish (US)
Pages (from-to)210-218
Number of pages9
JournalNeuroendocrinology
Volume80
Issue number4
DOIs
StatePublished - 2004

Fingerprint

Agouti-Related Protein
Appetite Regulation
Food
Sheep
Neuropeptide Y
Eating
Ruminants
Neurons
Arcuate Nucleus of Hypothalamus

Keywords

  • Agouti-related protein
  • Arcuate nucleus
  • c-Fos
  • Food intake
  • Neuropeptide Y
  • Ovine

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this

A role for agouti-related protein in appetite regulation in a species with continuous nutrient delivery. / Wagner, Christine G.; McMahon, Chris D.; Marks, Daniel; Daniel, Joseph A.; Steele, Barbara; Sartin, James L.

In: Neuroendocrinology, Vol. 80, No. 4, 2004, p. 210-218.

Research output: Contribution to journalArticle

Wagner, Christine G. ; McMahon, Chris D. ; Marks, Daniel ; Daniel, Joseph A. ; Steele, Barbara ; Sartin, James L. / A role for agouti-related protein in appetite regulation in a species with continuous nutrient delivery. In: Neuroendocrinology. 2004 ; Vol. 80, No. 4. pp. 210-218.
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