BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality.
<h4>Background/aims</h4>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 different...
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oai:doaj.org-article:ffe1798349a646ec9e836dd6d43dd9362021-11-18T08:55:08ZBMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality.1932-620310.1371/journal.pone.0074083https://doaj.org/article/ffe1798349a646ec9e836dd6d43dd9362013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24066098/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background/aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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.Mariëtte R BoonSjoerd A A van den BergYanan WangJan van den BosscheSofia KarkampounaMatthias BauwensMarijke De Saint-HubertGeertje van der HorstSlobodan VukicevicMenno P J de WintherLouis M HavekesJ Wouter JukemaJouke T TamsmaGabri van der PluijmKo Willems van DijkPatrick C N RensenPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e74083 (2013) |
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| spellingShingle |
Medicine R Science Q Mariëtte R Boon Sjoerd A A van den Berg Yanan Wang Jan van den Bossche Sofia Karkampouna Matthias Bauwens Marijke De Saint-Hubert Geertje van der Horst Slobodan Vukicevic Menno P J de Winther Louis M Havekes J Wouter Jukema Jouke T Tamsma Gabri van der Pluijm Ko Willems van Dijk Patrick C N Rensen BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| description |
<h4>Background/aims</h4>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.<h4>Methods and results</h4>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.<h4>Conclusion</h4>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. |
| format |
article |
| author |
Mariëtte R Boon Sjoerd A A van den Berg Yanan Wang Jan van den Bossche Sofia Karkampouna Matthias Bauwens Marijke De Saint-Hubert Geertje van der Horst Slobodan Vukicevic Menno P J de Winther Louis M Havekes J Wouter Jukema Jouke T Tamsma Gabri van der Pluijm Ko Willems van Dijk Patrick C N Rensen |
| author_facet |
Mariëtte R Boon Sjoerd A A van den Berg Yanan Wang Jan van den Bossche Sofia Karkampouna Matthias Bauwens Marijke De Saint-Hubert Geertje van der Horst Slobodan Vukicevic Menno P J de Winther Louis M Havekes J Wouter Jukema Jouke T Tamsma Gabri van der Pluijm Ko Willems van Dijk Patrick C N Rensen |
| author_sort |
Mariëtte R Boon |
| title |
BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| title_short |
BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| title_full |
BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| title_fullStr |
BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| title_full_unstemmed |
BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| title_sort |
bmp7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/ffe1798349a646ec9e836dd6d43dd936 |
| work_keys_str_mv |
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