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Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway
Open accessAbstract
Body weight is regulated by coordinating energy intake and energy expenditure. Transforming growth factor β (TGFβ)/bone morphogenetic protein (BMP) signaling has been shown to regulate energy balance in lower organisms, but whether a similar pathway exists in mammals is unknown. We have previously demonstrated that BMP7 can regulate brown adipogenesis and energy expenditure. In the current study, we have uncovered a novel role for BMP7 in appetite regulation. Systemic treatment of diet‐induced obese mice with BMP7 resulted in increased energy expenditure and decreased food intake, leading to a significant reduction in body weight and improvement of metabolic syndrome. Similar degrees of weight loss with reduced appetite were also observed in BMP7‐treated ob/ob mice, suggesting a leptin‐independent mechanism utilized by BMP7. Intracerebroventricular administration of BMP7 to mice led to an acute decrease in food intake, which was mediated, at least in part, by a central rapamycin‐sensitive mTOR‐p70S6 kinase pathway. Together, these results underscore the importance of BMP7 in regulating both food intake and energy expenditure, and suggest new therapeutic approaches for obesity and its comorbidities.— Townsend, K. L., Suzuki, R., Huang, T. L., Jing, E., Schulz, T. J., Lee, K., Taniguchi, C. M., Espinoza, D. O., McDougall, L. E., Zhang, H., He, T.‐C., Kokkotou, E., Tseng, Y.‐H. Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway. FASEB J. 26, 2187‐2196 (2012). www.fasebj.org
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“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 Townsend et al., 2012
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“…genes are those responding to nutrient levels ( Bmp7, Cd40, Aacs, Gclc, Nmur2, Cyp24a1, Adcyap1, Serpinc1, and Wnt11 ) (Sethi and Vidal-Puig, 2008; Peier et al., 2009; Townsend et al., 2012; Yi and Bishop, 2015; Shi and Tu, 2015; Toderici et al., 2016; Yasuda et al., 2021; Gastelum et al., 2021;)”
BackgroundKramer, K., Yang, J., Swanson, W. B., Hayano, S., Toda, M., Pan, H., Kim, J. K., Krebsbach, P. H., & Mishina, Y. M. (2018) · genesis · doi:10.1002/dvg.23220 · Cited by 17
“Taking into account the role mTOR plays in stem cell differentiation and proliferation in combination with the previously identified crosstalk between the mTOR and BMP signaling pathways (Agarwal et al., 2015; Langenfeld et al., 2005; Townsend et al., 2012) (Lee et al.”
BackgroundMa, H., Yuan, J., Ma, J., Ding, J., Lin, W., Wang, X., Zhang, M., Sun, Y., Wu, R., Liu, C., et al. (2019) · Journal of Endocrinology · doi:10.1530/joe-18-0693 · Cited by 14
Renaissance of brown adipose tissue research: integrating the old and new
Granneman, J. G. (2015) · International Journal of Obesity Supplements · doi:10.1038/ijosup.2015.3 · Cited by 12
Sehgal, P. B., Yang, Y., & Miller, E. J. (2015) · Molecular Medicine · doi:10.2119/molmed.2015.00122 · Cited by 14
Kim, B. Y., Choi, S. H., Kim, J., Ko, J., Yook, J. I., Kim, H. S., Lee, E. J., Kikkawa, D. O., & Yoon, J. S. (2022) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.63.6.7 · Cited by 12
Zhu, T., Chen, X., & Jiang, S. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1191278 · Cited by 12
“Most of the BAT-derived molecules, usually referred to as batokines, promote hypertrophy and hyperplasia of BAT, vascularization, innervation, and other processes that are all associated with BAT recruitment when thermogenic activity is enhanced (53, 54).”
BackgroundSyamsunarno, M. R. A. A., Alia, F., Anggraeni, N., Sumirat, V. A., Praptama, S., & Atik, N. (2021) · Veterinary World · doi:10.14202/vetworld.2021.1234-1240 · Cited by 12
“In ob/ob mice, the administration of BMP7-expressing adenovirus increased energy expenditure and decreased food intake, subsequently reducing BW by activating the central mTOR pathway in the hypothalamus, thus suggesting a leptin-independent pathway [14].”
BackgroundTownsend, K. L., Pritchard, E. M., Coburn, J. M., Kwon, Y. M., Blaszkiewicz, M., Lynes, M. D., Kaplan, D. L., & Tseng, Y. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.884601 · Cited by 11
DNA Methylation in the Hypothalamic Feeding Center and Obesity
Yoshikawa, C., Ariyani, W., & Kohno, D. (2023) · Journal of Obesity & Metabolic Syndrome · doi:10.7570/jomes23073 · Cited by 9
“The contribution of hypothalamic BMP7 to energy homeostasis has been reported, 52 although its precise role in AgRP neurons remains unclear.”
BackgroundZhong, S., Du, X., Gao, J., Ji, G., & Liu, Z. (2023) · Nutrients · doi:10.3390/nu16010064 · Cited by 9
Zhong, S., Wang, Y., Li, J., Wang, M., Li, M., Ma, Z., Zhang, S., & Liu, Z. (2017) · Gene Reports · doi:10.1016/j.genrep.2017.10.011 · Cited by 9
Kesharwani, D., & Brown, A. C. (2024) · Journal of Cellular Signaling · doi:10.33696/signaling.5.114 · Cited by 9
“Notably, administering BMP7 systemically to mice effectively counteracts obesity by enhancing energy expenditure and suppressing appetite [142].”
BackgroundCootes, T. A., Bhattacharyya, N. D., Huang, S. S. Y., Daniel, L., Bell-Anderson, K. S., Stifter, S. A., Chew, T., Solon‐Biet, S. M., Saraiva, L. R., Cai, Y., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111638 · Cited by 8
Das Fettgewebe – ein endokrines Organ
Blüher, M. (2014) · Der Internist · doi:10.1007/s00108-014-3456-3 · Cited by 10
Hypothalamic BMP9 suppresses glucose production by central PI3K/Akt/mTOR pathway
He, Y., Zhang, C., Luo, Y., Chen, J., Yang, M., Li, L., Gu, H. F., Yang, G., & Zhang, X. (2020) · Journal of Endocrinology · doi:10.1530/joe-19-0591 · Cited by 8
de la Puerta, R., Carcelén, M., Francés, R., de la Fuente, R., Hurlé, M. A., & Tramullas, M. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.104470 · Cited by 8
Ng, D. S. (2013) · Vitamins and hormones · doi:10.1016/b978-0-12-407766-9.00011-0 · Cited by 7
Insights into the adipose stem cell niche in health and disease
Brown, A. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819376-1.00012-3 · Cited by 4
Recent advances in brown adipose tissue biology
Shen, Y., Liu, X., Dong, M., Lin, J., Zhao, Q., Lee, H.-J., & Jin, W. (2014) · Chinese Science Bulletin · doi:10.1007/s11434-014-0386-3 · Cited by 4
Smith, C., Toit, R. D., & Ollewagen, T. (2023) · Inflammopharmacology · doi:10.1007/s10787-023-01321-x · Cited by 3
Adipokines, Inflammation, and Insulin Resistance in Obesity
Kwon, H., & Pessin, J. E. (2018) · Springer eBooks · doi:10.1007/978-3-319-89506-2_9 · Cited by 3
Tang, N., Li, Y., Wu, Y., Wu, H., Kang, Q., Yao, Q., Chen, S., Liu, Y., Jiang, K., Xiong, Y., et al. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.741594 · Cited by 1
Methodological Challenges for Ablation of BMPR1A in Hypothalamic Tanycytes—A Cautionary Tale
Tao, T., Leon-Palmer, N., DiPietro, S., & Townsend, K. L. (2026) · FASEB BioAdvances · doi:10.1096/fba.2025-00300 · Cited by 1
Zhang, J., Jiang, N., Wang, L., Cao, T.-B., Xie, Y., & Li, L. (2026) · Current Medical Science · doi:10.1007/s11596-026-00222-8 · Cited by 1
“Unexpectedly, systemic administration and ventricular injection of BMP7 both reduced appetite, resulting in 75% weight loss in diet-induced obese mice [58].”
Adipokine & klinische Bedeutung
Blüher, M. (2019) · Adipositas - Ursachen Folgeerkrankungen Therapie · doi:10.1055/a-0804-6353 · Cited by 1
“BMP7 scheint eine Rolle bei der Regulation des Appetitverhaltens zu spielen [43].”
BackgroundGhrelin, Lipid Metabolism, and Metabolic Syndrome
de Morentin, P. B. M., Tovar, S. A., Nogueiras, R., López, M., & Diéguez, C. (2013) · Wiley eBooks · doi:10.1002/9781118395318.ch29
Das Fettgewebe – ein endokrines Organ
Blüher, M. (2014) · Humanmedizin kompakt · doi:10.1007/s40355-014-0034-9
Grupos sanguíneos y transfusión en el lactante
Ron, E. J. (1945) · Acta pediátrica española/Acta pediátrica española
Kralisch, S., & Blüher, M. (2021) · Springer eBooks · doi:10.1007/978-3-030-57401-7_176
Kralisch, S., & Blüher, M. (2020) · Springer eBooks · doi:10.1007/978-3-030-21573-6_176-1
Grunz, E. A., Anderson, H., Ernst, R. M., Price, S., Good, D., Vieira‐Potter, V. J., & Parrish, A. R. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25116139
“BMPs were initially identified as regulators of bone morphogenesis but also have critical roles in embryonic development, tissue differentiation, metabolism, and cell proliferation [31–34].”
Background
Metadata
- Authors
- Townsend, K. L., Suzuki, R., Huang, T. L., Jing, E., Schulz, T. J., Lee, K., Taniguchi, C. M., Espinoza, D. O., McDougall, L. E., Zhang, H., He, T., Kokkotou, E., & Tseng, Y.
- Affiliations
- Joslin Diabetes Center (US)
- University of Chicago (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Kokkotou, Efi
- Tseng, Yu‐Hua
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-02-13
- Volume
- 26
- Issue
- 5
- Pages
- 2187-2196
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- PMC
- PMC3336788
- OpenAlex
- W2115947337
- Cited by
- 105
- References
- 61
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 9 · 2020: 5 · 2019: 9 · 2018: 8 · 2017: 6 · 2016: 9 · 2015: 8 · 2014: 13 · 2013: 13 · 2012: 2
- FWCI
- 5.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The FASEB Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (NIH R01 DK077097, UL1 RR 025758‐01, R01 DK080058, T32‐DK007260‐33, F32‐DK091996)
- Harvard Stem Cell Institute
- National Institute of Diabetes and Digestive and Kidney Diseases (P30‐DK036836)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- bone morphogenetic protein-7, obesity, appetite regulation, dietary intake, energy expenditure, mTOR signaling, p70 S6 kinase, TGF-β/BMP signaling, metabolic syndrome, brown adipogenesis, ob/ob mice, central nervous system
- MeSH terms
- Animals, Appetite, Cells, Cultured, Injections, Intraventricular, Obesity, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Mice, Bone Morphogenetic Protein 7, TOR Serine-Threonine Kinases
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