BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality

Folli, Franco and Boon, Mariëtte R. and van den Berg, Sjoerd A. A. and Wang, Yanan and van den Bossche, Jan and Karkampouna, Sofia and Bauwens, Matthias and De Saint-Hubert, Marijke and van der Horst, Geertje and Vukičević, Slobodan and de Winther, Menno P. J. and Havekes, Louis M. and Jukema, J. Wouter and Tamsma, Jouke T. and van der Pluijm, Gabri and van Dijk, Ko Willems and Rensen, Patrick C. N. (2013) BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. PLoS ONE, 8 (9). e74083. ISSN 1932-6203

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BACKGROUND/AIMS: Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. ----- METHODS AND RESULTS: High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21 °C or 28 °C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21 °C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28 °C. Additionally, BMP7 resulted in extensive 'browning' of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. ----- CONCLUSION: Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to combat obesity and associated disorders.

Item Type: Article
Additional Information: Copyright: © 2013 Boon et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
MeSH: Absorptiometry, Photon ; Adipose Tissue, Brown / metabolism ; Animals ; Bone Morphogenetic Protein 7 / genetics ; Bone Morphogenetic Protein 7 / metabolism ; Diet, High-Fat / adverse effects ; Energy Metabolism / physiology ; Male ; Mice ; Mice, Inbred C57BL ; Obesity / etiology ; Obesity / metabolism ; Temperature
Departments: Katedra za anatomiju i kliničku anatomiju
Depositing User: Marijan Šember
Status: Published
Boon, Mariëtte R.UNSPECIFIED
van den Berg, Sjoerd A. A.UNSPECIFIED
van den Bossche, JanUNSPECIFIED
Karkampouna, SofiaUNSPECIFIED
Bauwens, MatthiasUNSPECIFIED
De Saint-Hubert, MarijkeUNSPECIFIED
van der Horst, GeertjeUNSPECIFIED
Vukičević, SlobodanUNSPECIFIED
de Winther, Menno P. J.UNSPECIFIED
Havekes, Louis M.UNSPECIFIED
Jukema, J. WouterUNSPECIFIED
van der Pluijm, GabriUNSPECIFIED
van Dijk, Ko WillemsUNSPECIFIED
Rensen, Patrick C. N.UNSPECIFIED
Date: 16 September 2013
Date Deposited: 29 Jan 2014 10:02
Last Modified: 13 Jul 2020 08:05
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