Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice

Amanda M. Shaw; Boman G. Irani; Marcus C. Moore; Carrie Haskell-Luevano; William J. Millard

doi:10.1016/j.peptides.2004.12.026

Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice

Amanda M. Shaw, Boman G. Irani, Marcus C. Moore, Carrie Haskell-Luevano, William J. Millard

Medicinal Chemistry

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

46 Scopus citations

Abstract

Ghrelin stimulates food intake in part by activating hypothalamic neuropeptide Y (NPY) neurons/agouti related peptide (AGRP) neurons. We investigated the role of AGRP/melanocortin signaling in ghrelin-induced food intake by studying melanocortin 3 and 4 receptor knockout (MC3R KO and MC4R KO) mice. We also determined whether reduced ghrelin levels and/or an altered sensitivity to the GH-stimulating effects of ghrelin accompany the obesity syndromes of MC3R KO and MC4R KO mice. Compared to wild-type (WT) mice, the effects of ghrelin on food intake were reduced in MC3R KO and MC4R KO mice and circulating ghrelin levels were reduced in female MC4R KO mice. Female MC3R KO and MC4R KO mice exhibited a diminished responsiveness to the GH-releasing effects of ghrelin. Thus, deletion of the MC3R or MC4R results in a decreased sensitivity to ghrelin and verifies the involvement in the melanocortin system in ghrelin-induced food intake.

Original language	English (US)
Pages (from-to)	1720-1727
Number of pages	8
Journal	Peptides
Volume	26
Issue number	10
DOIs	https://doi.org/10.1016/j.peptides.2004.12.026
State	Published - Oct 2005

Bibliographical note

Funding Information:
The MC4R KO mice were originally provided by Dr. Dennis Huszar (Millennium Pharmaceuticals) and the MC3R KO mice were originally provided by Dr. Lex Van der Ploeg (Merck Research Laboratories). This work was supported by NIH Grants AG-10485 (WJM), DK-57080 (CH-L) and an American Heart Association predoctoral fellowship (BGI).

Keywords

Agouti related protein
Ghrelin
Growth hormone
Melanocortin
Orexigenic

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.peptides.2004.12.026

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title = "Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice",

abstract = "Ghrelin stimulates food intake in part by activating hypothalamic neuropeptide Y (NPY) neurons/agouti related peptide (AGRP) neurons. We investigated the role of AGRP/melanocortin signaling in ghrelin-induced food intake by studying melanocortin 3 and 4 receptor knockout (MC3R KO and MC4R KO) mice. We also determined whether reduced ghrelin levels and/or an altered sensitivity to the GH-stimulating effects of ghrelin accompany the obesity syndromes of MC3R KO and MC4R KO mice. Compared to wild-type (WT) mice, the effects of ghrelin on food intake were reduced in MC3R KO and MC4R KO mice and circulating ghrelin levels were reduced in female MC4R KO mice. Female MC3R KO and MC4R KO mice exhibited a diminished responsiveness to the GH-releasing effects of ghrelin. Thus, deletion of the MC3R or MC4R results in a decreased sensitivity to ghrelin and verifies the involvement in the melanocortin system in ghrelin-induced food intake.",

keywords = "Agouti related protein, Ghrelin, Growth hormone, Melanocortin, Orexigenic",

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note = "Funding Information: The MC4R KO mice were originally provided by Dr. Dennis Huszar (Millennium Pharmaceuticals) and the MC3R KO mice were originally provided by Dr. Lex Van der Ploeg (Merck Research Laboratories). This work was supported by NIH Grants AG-10485 (WJM), DK-57080 (CH-L) and an American Heart Association predoctoral fellowship (BGI).",

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AU - Haskell-Luevano, Carrie

AU - Millard, William J.

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N2 - Ghrelin stimulates food intake in part by activating hypothalamic neuropeptide Y (NPY) neurons/agouti related peptide (AGRP) neurons. We investigated the role of AGRP/melanocortin signaling in ghrelin-induced food intake by studying melanocortin 3 and 4 receptor knockout (MC3R KO and MC4R KO) mice. We also determined whether reduced ghrelin levels and/or an altered sensitivity to the GH-stimulating effects of ghrelin accompany the obesity syndromes of MC3R KO and MC4R KO mice. Compared to wild-type (WT) mice, the effects of ghrelin on food intake were reduced in MC3R KO and MC4R KO mice and circulating ghrelin levels were reduced in female MC4R KO mice. Female MC3R KO and MC4R KO mice exhibited a diminished responsiveness to the GH-releasing effects of ghrelin. Thus, deletion of the MC3R or MC4R results in a decreased sensitivity to ghrelin and verifies the involvement in the melanocortin system in ghrelin-induced food intake.

AB - Ghrelin stimulates food intake in part by activating hypothalamic neuropeptide Y (NPY) neurons/agouti related peptide (AGRP) neurons. We investigated the role of AGRP/melanocortin signaling in ghrelin-induced food intake by studying melanocortin 3 and 4 receptor knockout (MC3R KO and MC4R KO) mice. We also determined whether reduced ghrelin levels and/or an altered sensitivity to the GH-stimulating effects of ghrelin accompany the obesity syndromes of MC3R KO and MC4R KO mice. Compared to wild-type (WT) mice, the effects of ghrelin on food intake were reduced in MC3R KO and MC4R KO mice and circulating ghrelin levels were reduced in female MC4R KO mice. Female MC3R KO and MC4R KO mice exhibited a diminished responsiveness to the GH-releasing effects of ghrelin. Thus, deletion of the MC3R or MC4R results in a decreased sensitivity to ghrelin and verifies the involvement in the melanocortin system in ghrelin-induced food intake.

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KW - Orexigenic

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Ghrelin-induced food intake and growth hormone secretion are altered in melanocortin 3 and 4 receptor knockout mice

Abstract

Bibliographical note

Keywords

UN SDGs

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