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FASEB J. 2015 Apr;29(4):1414-25. doi: 10.1096/fj.14-261891. Epub 2014 Dec 30.

p38α function in osteoblasts influences adipose tissue homeostasis.

Author information

1
*Departamente de Ciències Fisiològiques II and and Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain; Institute for Research in Biomedicine, Barcelona, Spain; and Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain.
2
*Departamente de Ciències Fisiològiques II and and Departament de Patologia i Terapèutica Experimental, Universitat de Barcelona, Institut d'Investigació Biomèdica de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, Barcelona, Spain; Institute for Research in Biomedicine, Barcelona, Spain; and Centro de Investigación Biomédica en Red (CIBER) de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain fventura@ub.edu.

Abstract

The skeleton acts as an endocrine organ that regulates energy metabolism and calcium and phosphorous homeostasis through the secretion of osteocalcin (Oc) and fibroblast growth factor 23 (FGF23). However, evidence suggests that osteoblasts secrete additional unknown factors that contribute to the endocrine function of bone. To search for these additional factors, we generated mice with a conditional osteoblast-specific deletion of p38α MAPK known to display profound defects in bone homeostasis. Herein, we show that impaired osteoblast function is associated with a strong decrease in body weight and adiposity (P < 0.01). The differences in adiposity were not associated with diminished caloric intake, but rather reflected 20% increased energy expenditure and the up-regulation of uncoupling protein-1 (Ucp1) in white adipose tissue (WAT) and brown adipose tissue (BAT) (P < 0.05). These alterations in lipid metabolism and energy expenditure were correlated with a decrease in the blood levels of neuropeptide Y (NPY) (40% lower) rather than changes in the serum levels of insulin, Oc, or FGF23. Among all Npy-expressing tissues, only bone and primary osteoblasts showed a decline in Npy expression (P < 0.01). Moreover, the intraperitoneal administration of recombinant NPY partially restored the WAT weight and adipocyte size of p38α-deficient mice (P < 0.05). Altogether, these results further suggest that, in addition to Oc, other bone-derived signals affect WAT and energy expenditure contributing to the regulation of energy metabolism.

KEYWORDS:

NPY; adipocyte; bone; energy expenditure; metabolism; osteocalcin

PMID:
25550462
DOI:
10.1096/fj.14-261891
[Indexed for MEDLINE]

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