NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression: Potential roles of plasma insulin and leptin

Julie E. McMinn, Randy J. Seeley, Charles W. Wilkinson, Peter J Havel, Stephen C. Woods, Michael W. Schwartz

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

To test the hypothesis that NPY-induced overfeeding activates compensatory responses that inhibit hypothalamic NPY gene expression, we investigated the effect of chronically administered neuropeptide Y (NPY) on plasma hormones involved in energy balance and on the level of mRNA for hypothalamic neuropeptides. After cannulation of the third cerebral ventricle, male Long-Evans rats received a 4.5-day intracerebroventricular (icv) infusion of either human NPY (12 μg per day), or synthetic cerebrospinal fluid (CSF). NPY-treated animals were either allowed ad libitum access to food or were pairfed to the intake of CSF-treated controls. In rats fed ad libitum, icv NPY induced significant increases in food intake (75%), body weight (9%), plasma insulin (150%) and plasma leptin levels (300%) as compared to the icv CSF group. Levels of plasma leptin, but not insulin, remained elevated in NPY-treated rats that were pairfed to the intake of the CSF group. NPY mRNA levels in the midregion of the arcuate nucleus (ARC) were reduced by 50% in NPY-treated rats that were allowed to overeat, but not in the pairfed group, as determined by in situ hybridization. In contrast, mRNA for corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the rostral ARC were not significantly different among groups. These findings indicate that NPY-induced overfeeding suppresses ARC NPY mRNA expression, and that this effect unlikely to be mediated by a direct action of NPY, since it was abolished by limiting food intake in NPY-treated animals to that observed in controls. NPY-induced overfeeding was also associated with elevated plasma levels of leptin and insulin. The effect of these hormones to inhibit NPY gene expression may therefore have contributed to the decrease of NPY mRNA. Copyright (C) 1998 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)425-431
Number of pages7
JournalRegulatory Peptides
Volume75-76
DOIs
StatePublished - Sep 25 1998

Fingerprint

Neuropeptide Y
Leptin
Insulin
Plasmas
Messenger RNA
Cerebrospinal fluid
Arcuate Nucleus of Hypothalamus
Cerebrospinal Fluid
Rats
Gene expression
Animals
Eating
Hormones
Intraventricular Infusions
Gene Expression
Cerebral Ventricles
Pro-Opiomelanocortin
Long Evans Rats
Third Ventricle
Paraventricular Hypothalamic Nucleus

Keywords

  • Adipose tissue
  • Food intake
  • Hypothalamus
  • Neuropeptide
  • Obesity

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Neuroscience(all)

Cite this

NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression : Potential roles of plasma insulin and leptin. / McMinn, Julie E.; Seeley, Randy J.; Wilkinson, Charles W.; Havel, Peter J; Woods, Stephen C.; Schwartz, Michael W.

In: Regulatory Peptides, Vol. 75-76, 25.09.1998, p. 425-431.

Research output: Contribution to journalArticle

McMinn, Julie E. ; Seeley, Randy J. ; Wilkinson, Charles W. ; Havel, Peter J ; Woods, Stephen C. ; Schwartz, Michael W. / NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression : Potential roles of plasma insulin and leptin. In: Regulatory Peptides. 1998 ; Vol. 75-76. pp. 425-431.
@article{08369b789ee74a049e0e96da2cfe29d0,
title = "NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression: Potential roles of plasma insulin and leptin",
abstract = "To test the hypothesis that NPY-induced overfeeding activates compensatory responses that inhibit hypothalamic NPY gene expression, we investigated the effect of chronically administered neuropeptide Y (NPY) on plasma hormones involved in energy balance and on the level of mRNA for hypothalamic neuropeptides. After cannulation of the third cerebral ventricle, male Long-Evans rats received a 4.5-day intracerebroventricular (icv) infusion of either human NPY (12 μg per day), or synthetic cerebrospinal fluid (CSF). NPY-treated animals were either allowed ad libitum access to food or were pairfed to the intake of CSF-treated controls. In rats fed ad libitum, icv NPY induced significant increases in food intake (75{\%}), body weight (9{\%}), plasma insulin (150{\%}) and plasma leptin levels (300{\%}) as compared to the icv CSF group. Levels of plasma leptin, but not insulin, remained elevated in NPY-treated rats that were pairfed to the intake of the CSF group. NPY mRNA levels in the midregion of the arcuate nucleus (ARC) were reduced by 50{\%} in NPY-treated rats that were allowed to overeat, but not in the pairfed group, as determined by in situ hybridization. In contrast, mRNA for corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the rostral ARC were not significantly different among groups. These findings indicate that NPY-induced overfeeding suppresses ARC NPY mRNA expression, and that this effect unlikely to be mediated by a direct action of NPY, since it was abolished by limiting food intake in NPY-treated animals to that observed in controls. NPY-induced overfeeding was also associated with elevated plasma levels of leptin and insulin. The effect of these hormones to inhibit NPY gene expression may therefore have contributed to the decrease of NPY mRNA. Copyright (C) 1998 Elsevier Science B.V.",
keywords = "Adipose tissue, Food intake, Hypothalamus, Neuropeptide, Obesity",
author = "McMinn, {Julie E.} and Seeley, {Randy J.} and Wilkinson, {Charles W.} and Havel, {Peter J} and Woods, {Stephen C.} and Schwartz, {Michael W.}",
year = "1998",
month = "9",
day = "25",
doi = "10.1016/S0167-0115(98)00098-6",
language = "English (US)",
volume = "75-76",
pages = "425--431",
journal = "Regulatory Peptides",
issn = "0167-0115",
publisher = "Elsevier",

}

TY - JOUR

T1 - NPY-induced overfeeding suppresses hypothalamic NPY mRNA expression

T2 - Potential roles of plasma insulin and leptin

AU - McMinn, Julie E.

AU - Seeley, Randy J.

AU - Wilkinson, Charles W.

AU - Havel, Peter J

AU - Woods, Stephen C.

AU - Schwartz, Michael W.

PY - 1998/9/25

Y1 - 1998/9/25

N2 - To test the hypothesis that NPY-induced overfeeding activates compensatory responses that inhibit hypothalamic NPY gene expression, we investigated the effect of chronically administered neuropeptide Y (NPY) on plasma hormones involved in energy balance and on the level of mRNA for hypothalamic neuropeptides. After cannulation of the third cerebral ventricle, male Long-Evans rats received a 4.5-day intracerebroventricular (icv) infusion of either human NPY (12 μg per day), or synthetic cerebrospinal fluid (CSF). NPY-treated animals were either allowed ad libitum access to food or were pairfed to the intake of CSF-treated controls. In rats fed ad libitum, icv NPY induced significant increases in food intake (75%), body weight (9%), plasma insulin (150%) and plasma leptin levels (300%) as compared to the icv CSF group. Levels of plasma leptin, but not insulin, remained elevated in NPY-treated rats that were pairfed to the intake of the CSF group. NPY mRNA levels in the midregion of the arcuate nucleus (ARC) were reduced by 50% in NPY-treated rats that were allowed to overeat, but not in the pairfed group, as determined by in situ hybridization. In contrast, mRNA for corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the rostral ARC were not significantly different among groups. These findings indicate that NPY-induced overfeeding suppresses ARC NPY mRNA expression, and that this effect unlikely to be mediated by a direct action of NPY, since it was abolished by limiting food intake in NPY-treated animals to that observed in controls. NPY-induced overfeeding was also associated with elevated plasma levels of leptin and insulin. The effect of these hormones to inhibit NPY gene expression may therefore have contributed to the decrease of NPY mRNA. Copyright (C) 1998 Elsevier Science B.V.

AB - To test the hypothesis that NPY-induced overfeeding activates compensatory responses that inhibit hypothalamic NPY gene expression, we investigated the effect of chronically administered neuropeptide Y (NPY) on plasma hormones involved in energy balance and on the level of mRNA for hypothalamic neuropeptides. After cannulation of the third cerebral ventricle, male Long-Evans rats received a 4.5-day intracerebroventricular (icv) infusion of either human NPY (12 μg per day), or synthetic cerebrospinal fluid (CSF). NPY-treated animals were either allowed ad libitum access to food or were pairfed to the intake of CSF-treated controls. In rats fed ad libitum, icv NPY induced significant increases in food intake (75%), body weight (9%), plasma insulin (150%) and plasma leptin levels (300%) as compared to the icv CSF group. Levels of plasma leptin, but not insulin, remained elevated in NPY-treated rats that were pairfed to the intake of the CSF group. NPY mRNA levels in the midregion of the arcuate nucleus (ARC) were reduced by 50% in NPY-treated rats that were allowed to overeat, but not in the pairfed group, as determined by in situ hybridization. In contrast, mRNA for corticotropin-releasing hormone (CRH) in the paraventricular nucleus (PVN) and proopiomelanocortin (POMC) in the rostral ARC were not significantly different among groups. These findings indicate that NPY-induced overfeeding suppresses ARC NPY mRNA expression, and that this effect unlikely to be mediated by a direct action of NPY, since it was abolished by limiting food intake in NPY-treated animals to that observed in controls. NPY-induced overfeeding was also associated with elevated plasma levels of leptin and insulin. The effect of these hormones to inhibit NPY gene expression may therefore have contributed to the decrease of NPY mRNA. Copyright (C) 1998 Elsevier Science B.V.

KW - Adipose tissue

KW - Food intake

KW - Hypothalamus

KW - Neuropeptide

KW - Obesity

UR - http://www.scopus.com/inward/record.url?scp=0032566799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032566799&partnerID=8YFLogxK

U2 - 10.1016/S0167-0115(98)00098-6

DO - 10.1016/S0167-0115(98)00098-6

M3 - Article

C2 - 9802439

AN - SCOPUS:0032566799

VL - 75-76

SP - 425

EP - 431

JO - Regulatory Peptides

JF - Regulatory Peptides

SN - 0167-0115

ER -