BMP4 Gene Therapy in Mature Mice Reduces BAT Activation but Protects from Obesity by Browning Subcutaneous Adipose Tissue
Hoffmann, Jenny M. (University of Gothenburg)
Grünberg, John (University of Cambridge)
Church, Christopher (Cardiovascular and Metabolic Disease, MedImmune, Granta Park, Cambridge)
Elias Puigdomenech, Ivet (Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas)
Palsdottir, Vilborg (University of Gothenburg)
Jansson, John-Olov (University of Gothenburg)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Hammarstedt, Ann (University of Gothenburg)
Hedjazifar, Shahram (University of Gothenburg)
Smith, Ulf (University of Gothenburg)
Universitat Autònoma de Barcelona

Data:	2017
Resum:	We examined the effect of Bone Morphogenetic Protein 4 (BMP4) on energy expenditure in adult mature mice by targeting the liver with adeno-associated viral (AAV) BMP4 vectors to increase circulating levels. We verified the direct effect of BMP4 in inducing a brown oxidative phenotype in differentiating preadipocytes in vitro. AAV-BMP4-treated mice display marked browning of subcutaneous adipocytes, with increased mitochondria and Uncoupling Protein 1 (UCP1). These mice are protected from obesity on a high-fat diet and have increased whole-body energy expenditure, improved insulin sensitivity, reduced liver fat, and reduced adipose tissue inflammation. On a control diet, they show unchanged body weight but improved insulin sensitivity. In contrast, AAV-BMP4-treated mice showed beiging of BAT with reduced UCP1, increased lipids, and reduced hormone-sensitive lipase (HSL). Thus, BMP4 exerts different effects on WAT and BAT, but the overall effect is to enhance insulin sensitivity and whole-body energy expenditure by browning subcutaneous adipose tissue.
Ajuts:	Ministerio de Economía y Competitividad 2014-54866-R
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Cell reports, Vol. 20, Num. 5 (August 2017) , p. 1038-1049, ISSN 2211-1247

DOI: 10.1016/j.celrep.2017.07.020
PMID: 28768190

13 p, 4.6 MB

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