Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure

C. J. Small; Y. L. Liu; S. A. Stanley; I. P. Connoley; A. Kennedy; M. J. Stock; S. R. Bloom

doi:10.1038/sj.ijo.0802253

Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure

C. J. Small
, Y. L. Liu
, S. A. Stanley
, I. P. Connoley
, A. Kennedy
, M. J. Stock
, S. R. Bloom

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure. DESIGN: A 7-day intracerebroventricular administration of Agrp (1 nmol/day) in rats. MEASUREMENTS: Oxygen consumption was determined in closed-circuit respirometers on days 1 and 8. BRL-35135, a β3-adrenoreceptor agonist known to activate the brown adipose tissue (BAT) thermogenesis directly and increase core temperature, was administered i.p. (40 μg/kg) on day 9 to challenge functionally the BAT. RESULTS: Agrp treatment caused a 54% increase in daily food intake and a 12% increase in body weight. An 8% decrease in VO₂ measurements was observed following ICV Agrp treatment on day 1. A similar decrease (7%) was observed on day 8. BRL-35135 stimulated colonic temperature in control rats. However, in the rats that had previously been treated with Agrp this effect was significantly blunted. CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy. The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake.

Original language	English
Pages (from-to)	530-533
Number of pages	4
Journal	International Journal of Obesity
Volume	27
Issue number	4
DOIs	https://doi.org/10.1038/sj.ijo.0802253
State	Published - 1 Apr 2003
Externally published	Yes

Keywords

Brown adipose tissue (BAT)
Hypothalamus
MC4 receptor
Melanocortin
Oxygen consumption
Uncoupling protein-1 (UCP-1)

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10.1038/sj.ijo.0802253

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title = "Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure",

abstract = "OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure. DESIGN: A 7-day intracerebroventricular administration of Agrp (1 nmol/day) in rats. MEASUREMENTS: Oxygen consumption was determined in closed-circuit respirometers on days 1 and 8. BRL-35135, a β3-adrenoreceptor agonist known to activate the brown adipose tissue (BAT) thermogenesis directly and increase core temperature, was administered i.p. (40 μg/kg) on day 9 to challenge functionally the BAT. RESULTS: Agrp treatment caused a 54\% increase in daily food intake and a 12\% increase in body weight. An 8\% decrease in VO2 measurements was observed following ICV Agrp treatment on day 1. A similar decrease (7\%) was observed on day 8. BRL-35135 stimulated colonic temperature in control rats. However, in the rats that had previously been treated with Agrp this effect was significantly blunted. CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy. The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake.",

keywords = "Brown adipose tissue (BAT), Hypothalamus, MC4 receptor, Melanocortin, Oxygen consumption, Uncoupling protein-1 (UCP-1)",

author = "Small, \{C. J.\} and Liu, \{Y. L.\} and Stanley, \{S. A.\} and Connoley, \{I. P.\} and A. Kennedy and Stock, \{M. J.\} and Bloom, \{S. R.\}",

note = "Funding Information: This work is funded by a Medical Council Research (MRC) programme grant (SR Bloom, MA Ghatei, CJ Small, G7811974). This work was conducted as a collaborative research project. The authors acknowledge Professor Stock for his input into this work and for his expert guidance. We dedicate this manuscript to him.",

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doi = "10.1038/sj.ijo.0802253",

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T1 - Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure

AU - Small, C. J.

AU - Liu, Y. L.

AU - Stanley, S. A.

AU - Connoley, I. P.

AU - Kennedy, A.

AU - Stock, M. J.

AU - Bloom, S. R.

N1 - Funding Information: This work is funded by a Medical Council Research (MRC) programme grant (SR Bloom, MA Ghatei, CJ Small, G7811974). This work was conducted as a collaborative research project. The authors acknowledge Professor Stock for his input into this work and for his expert guidance. We dedicate this manuscript to him.

PY - 2003/4/1

Y1 - 2003/4/1

N2 - OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure. DESIGN: A 7-day intracerebroventricular administration of Agrp (1 nmol/day) in rats. MEASUREMENTS: Oxygen consumption was determined in closed-circuit respirometers on days 1 and 8. BRL-35135, a β3-adrenoreceptor agonist known to activate the brown adipose tissue (BAT) thermogenesis directly and increase core temperature, was administered i.p. (40 μg/kg) on day 9 to challenge functionally the BAT. RESULTS: Agrp treatment caused a 54% increase in daily food intake and a 12% increase in body weight. An 8% decrease in VO2 measurements was observed following ICV Agrp treatment on day 1. A similar decrease (7%) was observed on day 8. BRL-35135 stimulated colonic temperature in control rats. However, in the rats that had previously been treated with Agrp this effect was significantly blunted. CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy. The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake.

AB - OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure. DESIGN: A 7-day intracerebroventricular administration of Agrp (1 nmol/day) in rats. MEASUREMENTS: Oxygen consumption was determined in closed-circuit respirometers on days 1 and 8. BRL-35135, a β3-adrenoreceptor agonist known to activate the brown adipose tissue (BAT) thermogenesis directly and increase core temperature, was administered i.p. (40 μg/kg) on day 9 to challenge functionally the BAT. RESULTS: Agrp treatment caused a 54% increase in daily food intake and a 12% increase in body weight. An 8% decrease in VO2 measurements was observed following ICV Agrp treatment on day 1. A similar decrease (7%) was observed on day 8. BRL-35135 stimulated colonic temperature in control rats. However, in the rats that had previously been treated with Agrp this effect was significantly blunted. CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy. The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake.

KW - Brown adipose tissue (BAT)

KW - Hypothalamus

KW - MC4 receptor

KW - Melanocortin

KW - Oxygen consumption

KW - Uncoupling protein-1 (UCP-1)

UR - https://www.scopus.com/pages/publications/0041944526

U2 - 10.1038/sj.ijo.0802253

DO - 10.1038/sj.ijo.0802253

M3 - Article

C2 - 12664087

AN - SCOPUS:0041944526

SN - 0307-0565

VL - 27

SP - 530

EP - 533

JO - International Journal of Obesity

JF - International Journal of Obesity

IS - 4

ER -

Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure

Abstract

Keywords

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