title: Androgens modulate osteocalcin release by human visceral adipose tissue.
abstract: OBJECTIVE
  Androgens inhibit adipogenic differentiation through an androgen receptor (AR)-mediated pathway, increase lipolysis and reduce lipid accumulation in adipocytes. Undercarboxylated osteocalcin (ucOCN) regulates insulin and adiponectin secretion and is released by adipose tissue (AT). Our objective was to investigate, ex vivo and in vivo, the role of androgens on osteocalcin (OCN) modulation in human AT. DesiGN, PATIENTS, SETTING: Omental AT (OAT) for in vitro study and blood samples from 91 male patients of Padova University Hospital were used.
  
  
  METHODS
  Omental AT was treated with dihydrotestosterone (DHT) in presence and in absence of flutamide. cOCN and ucOCN release by AT in a simple growth medium was evaluated by ELISA. OCN, both undercarboxylated (ucOCN) and carboxylated (cOCN) forms, was measured in serum by ELISA.
  
  
  RESULTS
  After 24-h DHT stimulation, the release of both cOCN and ucOCN by OAT was statistically increased (P < 0·05). Co-incubation with flutamide blunted OCN production. Overweight and obese patients had lower total and free testosterone (T), associated with lower ucOCN and ucOCN/OCN ratio. Free T was negatively correlated to BMI (ρ = -0·706, P < 0·05) and positively correlated to ucOCN/OCN ratio (ρ = 0·223, P < 0·05).
  
  
  CONCLUSIONS
  Our data suggest that androgens modulate OCN release by OAT in vitro. In addition to the anti-adipogenic role of androgens, they support a novel mechanism by which androgens could exert a protective effect in energy metabolism. This hypothesis appears even more significant considering that sexual hormones' levels are greatly altered in obesity and that AT is both highly involved in their clearance and able to produce OCN.
authors.affiliation: Department of Histology, Microbiology and Medical Biotechnologies, Section of Clinical Pathology and Centre for Male Gamete CryopreservationEndocrine-Metabolic Laboratory (A.S.), Internal Medicine 3, University of PadovaEURAC Institute of Mountain Emergency Medicine (G.S.), Bozen/BolzanoDepartment of Oncological and Surgical Sciences, Clinical Surgery II (A.B), University Hospital of PadovaDepartment of Laboratory Medicine (M.P.), University Hospital of Padova, Padova, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Foresta
authors.forename: Giacomo
authors.initials: G
authors.lastname: Strapazzon
authors.forename: Luca
authors.initials: L
authors.lastname: De Toni
authors.forename: Lisa
authors.initials: L
authors.lastname: Gianesello
authors.forename: Andrea
authors.initials: A
authors.lastname: Bruttocao
authors.forename: Alessandro
authors.initials: A
authors.lastname: Scarda
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Andrea
authors.initials: A
authors.lastname: Garolla
mesh_terms: D000328:Adult; D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D005485:Flutamide / Q000494:pharmacology; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D015675:Osteocalcin / Q000378:metabolism*; D050177:Overweight / Q000097:blood / Q000378:metabolism*; D013739:Testosterone / Q000097:blood*
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D013196:Dihydrotestosterone; D015675:Osteocalcin; D013739:Testosterone; D005485:Flutamide