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p38α function in osteoblasts influences adipose tissue homeostasis
Author(s) -
RodríguezCarballo Edgardo,
Gámez Beatriz,
MéndezLucas Andrés,
SánchezFreutrie Manuela,
Zorzano Antonio,
Bartrons Ramon,
Alcántara Soledad,
Perales José Carlos,
Ventura Francesc
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.14-261891
Subject(s) - adipose tissue , homeostasis , function (biology) , microbiology and biotechnology , medicine , endocrinology , chemistry , biology
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 bodyweight 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.—Rodríguez‐Carballo, E., Gámez, B., Méndez‐Lucas, A., Sánchez‐Freutrie, M., Zorzano, A., Bartrons, R., Alcántara, S., Perales, J. C., Ventura, F. p38α function in osteoblasts influences adipose tissue homeostasis. FASEB J. 29, 1414‐1425 (2015). www.fasebj.org