Evidence for osteocalcin production by adipose tissue and its role in human metabolism.
BACKGROUND
The adipose tissue (AT), which is an endocrine organ, is linked to several metabolic abnormalities. Undercarboxylated osteocalcin (ucOCN) regulates insulin and adiponectin secretion.


OBJECTIVE
Our objective was to investigate the involvement of OCN in obesity and to evaluate, in vitro and ex vivo, the role of AT in the modulation of this endocrine circuit.


METHODS
This transversal study involved 83 male subjects, divided according to the World Health Organization body mass index classification, evaluated at Padova's Obesity Outpatient Clinic.


METHODS
OCN, both undercarboxylated (ucOCN) and carboxylated (cOCN) forms, was measured in serum by ELISA. OCN mRNA expression and protein production were measured by quantitative RT-PCR and immunohistochemistry during in vitro adipogenesis and in sc AT (SAT) and omental AT (OAT) from normal adult men. cOCN and ucOCN release by AT in a simple growth medium was verified by ELISA.


RESULTS
Overweight and obese patients had a lower ucOCN and ucOC/OCN ratio. In the whole cohort, ucOCN/OCN ratio was negatively correlated to body mass index (rho = -0.233; P < 0.05). OCN mRNA was present in SAT and OAT and during all stages of adipogenesis, with higher expression in the first steps. Immunohistochemistry confirmed the expression of OCN protein. Both SAT and OAT were able to release cOCN and ucOCN.


CONCLUSIONS
Our data support a pathophysiological link between ucOCN and cOCN balance and obesity. OCN is present in the first phases of adipogenesis but also in human AT ex vivo. AT releases, in vitro, both ucOCN and cOCN, suggesting a possible link between AT and OCN in the regulation of metabolism.
Foresta
Carlo
C
Department of Histology, Internal Medicine 3, University of Padova, Italy. carlo.foresta@unipd.it
Strapazzon
Giacomo
G
De Toni
Luca
L
Gianesello
Lisa
L
Calcagno
Alessandra
A
Pilon
Catia
C
Plebani
Mario
M
Vettor
Roberto
R
D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000378:metabolism*; D015992:Body Mass Index; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism*; D050177:Overweight / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
D012333:RNA, Messenger; D015675:Osteocalcin