BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions
Open accessAbstract
Thermogenesis in brown adipose tissue (BAT) is fundamental to energy balance and is also relevant for humans. Bone morphogenetic proteins (BMPs) regulate adipogenesis, and, here, we describe a role for BMP8B in the direct regulation of thermogenesis. BMP8B is induced by nutritional and thermogenic factors in mature BAT, increasing the response to noradrenaline through enhanced p38MAPK/CREB signaling and increased lipase activity. Bmp8b(-/-) mice exhibit impaired thermogenesis and reduced metabolic rate, causing weight gain despite hypophagia. BMP8B is also expressed in the hypothalamus, and Bmp8b(-/-) mice display altered neuropeptide levels and reduced phosphorylation of AMP-activated protein kinase (AMPK), indicating an anorexigenic state. Central BMP8B treatment increased sympathetic activation of BAT, dependent on the status of AMPK in key hypothalamic nuclei. Our results indicate that BMP8B is a thermogenic protein that regulates energy balance in partnership with hypothalamic AMPK. BMP8B may offer a mechanism to specifically increase energy dissipation by BAT.
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Macrophages and the bone morphogenetic protein BMP8B have the capacity to regulate BAT thermogenesis.
“In addition, recent articles reported that macrophages ([125](#B125)) and the bone morphogenetic protein BMP8B ([172](#B172)) have also the capacity to regulate BAT thermogenesis.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [172]
BMP8b can also be produced in BAT and promote NE signaling locally, activating MAPK pathway and lipolysis in brown adipocytes.
“Interestingly, BMP8b can also be produced in BAT and promote NE signaling locally, activating the MAPK pathway and lipolysis in brown adipocytes 80.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [80]
BMP8B increases neuronal activation in the LHA.
“Given that BMP8B acts centrally, its thermogenic effect is dependent upon the activation status of AMPK in the VMH, and it increases neuronal activation in the LHA (Whittle et al., 2012), we aimed to uncover the neuronal circuitry linking energy sensors and neuropeptides involved in the thermogenic effect of central BMP8B.”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
BMP7 and BMP8B regulate BAT thermogenic function and increase EE.
“Thus, BMP7 and BMP8B were demonstrated to regulate BAT thermogenic function and increase EE (Tseng et al., 2008, Townsend et al., 2012, Townsend et al., 2013, Whittle et al., 2012).”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
BMP8B acts centrally.
“Given that BMP8B acts centrally, its thermogenic effect is dependent upon the activation status of AMPK in the VMH, and it increases neuronal activation in the LHA (Whittle et al., 2012), we aimed to uncover the neuronal circuitry linking energy sensors and neuropeptides involved in the thermogenic effect of central BMP8B.”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
AMPK in the VMH and OX in the LHA modulate BAT thermogenesis.
“AMP-activated protein kinase (AMPK) in the ventromedial nucleus of the hypothalamus (VMH) and orexin (OX) in the lateral hypothalamic area (LHA) modulate brown adipose tissue (BAT) thermogenesis.”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
BMP8B's thermogenic effect is dependent upon the activation status of AMPK in the VMH.
“Given that BMP8B acts centrally, its thermogenic effect is dependent upon the activation status of AMPK in the VMH, and it increases neuronal activation in the LHA (Whittle et al., 2012), we aimed to uncover the neuronal circuitry linking energy sensors and neuropeptides involved in the thermogenic effect of central BMP8B.”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
Central BMP8B exerts a robust thermogenic effect in females.
“Recent evidence has demonstrated that central BMP8B exerts a robust thermogenic effect in females (Whittle et al., 2012).”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
BMP8B in the VMH recapitulated the effect of its central i.c.v. administration.
“Our data showed that administration of BMP8B within the VMH recapitulated the effect of its central (i.c.v.) administration (Whittle et al., 2012), namely feeding-independent weight loss, increased EE and BAT thermogenesis, and reduced RQ, in association with reduced AMPK signaling in the VMH and elevated BAT UCP1 protein content as well as browning of WAT.”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Whittle et al., 2012
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- Authors
- Whittle, A. J., Carobbio, S., Martins, L., Slawik, M., Hondares, E., Vázquez, M. J., Morgan, D., Csikasz, R. I., Gallego, R., Rodriguez-Cuenca, S., Dale, M., Virtue, S., Villarroya, F., Cannon, B., Rahmouni, K., López, M., & Vidal-Puig, A.
- Affiliations
- University of Cambridge (GB)
- Universidade de Santiago de Compostela (ES)
- Centro de Investigación Biomédica en Red (ES)
- University of Iowa (US)
- Stockholm University (SE)
- Royal Veterinary College (GB)
- Corresponding author
- Whittle, Andrew J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 149
- Issue
- 4
- Pages
- 871-885
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3383997
- OpenAlex
- W2100538674
- Cited by
- 573
- References
- 61
- Citations by year
- 2026: 19 · 2025: 22 · 2024: 25 · 2023: 23 · 2022: 30 · 2021: 43 · 2020: 48 · 2019: 39 · 2018: 48 · 2017: 48 · 2016: 52 · 2015: 65 · 2014: 50 · 2013: 47 · 2012: 12
- FWCI
- 37.01
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- RUNA. Repositorio Institucional del Sergas (Servicio Gallego de Salud (SERGAS)) (submittedVersion, cc-by)
- Funders
- Wellcome Trust
- Biotechnology and Biological Sciences Research Council (BB/J009865/1)
- National Heart, Lung, and Blood Institute (HL-084207, P01HL084207)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- BMP8B, brown adipose tissue, thermogenesis, bone morphogenetic proteins, norepinephrine, lipase activity, hypothalamus, AMPK, sympathetic nervous system, energy balance, weight gain, anorexigenic peptides, energy dissipation
- MeSH terms
- Animals, Adipose Tissue, Brown, Diet, Energy Metabolism, Female, Hypothalamus, Mice, Inbred C57BL, Norepinephrine, Obesity, Rats, Sprague-Dawley, Bone Morphogenetic Proteins, Thermogenesis, Adipogenesis, Mice, Rats, AMP-Activated Protein Kinases
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