Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A

Kristy L. Townsend, Christopher (Chris) Madden, Magdalena Blaszkiewicz, Lindsay McDougall, Domenico Tupone, Matthew D. Lynes, Yuji Mishina, Paul Yu, Shaun Morrison, Yu Hua Tseng

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein (BMP) 7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibited a lack of obesity, even on a 45% high-fat diet. This is because the brown adipose tissue (BAT) of KO animals exhibited increased sympathetic activation and greater thermogenic capacity owing to a reestablishment of energy balance, most likely stemming from a compensatory increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals given central BMP7 displayed increased energy expenditure and a specific increase in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy expenditure or BAT SNA. Together, we demonstrated an important role for hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A-mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD regulation of the sympathetic drive to BAT for thermogenesis.

Original languageEnglish (US)
Pages (from-to)4233-4245
Number of pages13
JournalEndocrinology
Volume158
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Pro-Opiomelanocortin
Brown Adipose Tissue
Neurons
Bone Morphogenetic Proteins
Knockout Mice
Appetite Regulation
Energy Metabolism
Type I Bone Morphogenetic Protein Receptors
Bone Morphogenetic Protein 7
Appetite Depressants
Aptitude
Thermogenesis
High Fat Diet
Appetite
Hypothalamus
Obesity
Pharmacology
Brain

ASJC Scopus subject areas

  • Endocrinology

Cite this

Townsend, K. L., Madden, C. C., Blaszkiewicz, M., McDougall, L., Tupone, D., Lynes, M. D., ... Tseng, Y. H. (2017). Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A. Endocrinology, 158(12), 4233-4245. https://doi.org/10.1210/en.2017-00212

Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A. / Townsend, Kristy L.; Madden, Christopher (Chris); Blaszkiewicz, Magdalena; McDougall, Lindsay; Tupone, Domenico; Lynes, Matthew D.; Mishina, Yuji; Yu, Paul; Morrison, Shaun; Tseng, Yu Hua.

In: Endocrinology, Vol. 158, No. 12, 01.12.2017, p. 4233-4245.

Research output: Contribution to journalArticle

Townsend, KL, Madden, CC, Blaszkiewicz, M, McDougall, L, Tupone, D, Lynes, MD, Mishina, Y, Yu, P, Morrison, S & Tseng, YH 2017, 'Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A', Endocrinology, vol. 158, no. 12, pp. 4233-4245. https://doi.org/10.1210/en.2017-00212
Townsend, Kristy L. ; Madden, Christopher (Chris) ; Blaszkiewicz, Magdalena ; McDougall, Lindsay ; Tupone, Domenico ; Lynes, Matthew D. ; Mishina, Yuji ; Yu, Paul ; Morrison, Shaun ; Tseng, Yu Hua. / Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A. In: Endocrinology. 2017 ; Vol. 158, No. 12. pp. 4233-4245.
@article{0e938e7d92fd4da2a190f731f4ca4d08,
title = "Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A",
abstract = "The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein (BMP) 7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibited a lack of obesity, even on a 45{\%} high-fat diet. This is because the brown adipose tissue (BAT) of KO animals exhibited increased sympathetic activation and greater thermogenic capacity owing to a reestablishment of energy balance, most likely stemming from a compensatory increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals given central BMP7 displayed increased energy expenditure and a specific increase in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy expenditure or BAT SNA. Together, we demonstrated an important role for hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A-mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD regulation of the sympathetic drive to BAT for thermogenesis.",
author = "Townsend, {Kristy L.} and Madden, {Christopher (Chris)} and Magdalena Blaszkiewicz and Lindsay McDougall and Domenico Tupone and Lynes, {Matthew D.} and Yuji Mishina and Paul Yu and Shaun Morrison and Tseng, {Yu Hua}",
year = "2017",
month = "12",
day = "1",
doi = "10.1210/en.2017-00212",
language = "English (US)",
volume = "158",
pages = "4233--4245",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "12",

}

TY - JOUR

T1 - Reestablishment of Energy Balance in a Male Mouse Model With POMC Neuron Deletion of BMPR1A

AU - Townsend, Kristy L.

AU - Madden, Christopher (Chris)

AU - Blaszkiewicz, Magdalena

AU - McDougall, Lindsay

AU - Tupone, Domenico

AU - Lynes, Matthew D.

AU - Mishina, Yuji

AU - Yu, Paul

AU - Morrison, Shaun

AU - Tseng, Yu Hua

PY - 2017/12/1

Y1 - 2017/12/1

N2 - The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein (BMP) 7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibited a lack of obesity, even on a 45% high-fat diet. This is because the brown adipose tissue (BAT) of KO animals exhibited increased sympathetic activation and greater thermogenic capacity owing to a reestablishment of energy balance, most likely stemming from a compensatory increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals given central BMP7 displayed increased energy expenditure and a specific increase in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy expenditure or BAT SNA. Together, we demonstrated an important role for hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A-mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD regulation of the sympathetic drive to BAT for thermogenesis.

AB - The regulation of energy balance involves complex processes in the brain, including coordination by hypothalamic neurons that contain pro-opiomelanocortin (POMC). We previously demonstrated that central bone morphogenetic protein (BMP) 7 reduced appetite. Now we show that a type 1 BMP receptor, BMPR1A, is colocalized with POMC neurons and that POMC-BMPR1A-knockout (KO) mice are hyperphagic, revealing physiological involvement of BMP signaling in anorectic POMC neurons in the regulation of appetite. Surprisingly, the hyperphagic POMC-BMPR1A-KO mice exhibited a lack of obesity, even on a 45% high-fat diet. This is because the brown adipose tissue (BAT) of KO animals exhibited increased sympathetic activation and greater thermogenic capacity owing to a reestablishment of energy balance, most likely stemming from a compensatory increase of BMPR1A in the whole hypothalamus of KO mice. Indeed, control animals given central BMP7 displayed increased energy expenditure and a specific increase in sympathetic nerve activity (SNA) in BAT. In these animals, pharmacological blockade of BMPR1A-SMAD signaling blunted the ability of BMP7 to increase energy expenditure or BAT SNA. Together, we demonstrated an important role for hypothalamic BMP signaling in the regulation of energy balance, including BMPR1A-mediated appetite regulation in POMC neurons as well as hypothalamic BMP-SMAD regulation of the sympathetic drive to BAT for thermogenesis.

UR - http://www.scopus.com/inward/record.url?scp=85038401237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85038401237&partnerID=8YFLogxK

U2 - 10.1210/en.2017-00212

DO - 10.1210/en.2017-00212

M3 - Article

C2 - 29040444

AN - SCOPUS:85038401237

VL - 158

SP - 4233

EP - 4245

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 12

ER -